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S  Scientific  Library 


UNITED  STATES  PATENT  OFFICE 


Case 


M. 


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J  J,  to  /  7 

THE 

american 
Journal  of  Pharmacy 

PUBLISHED  BY  AUTHORITY  OF  THE 

PHILADELPHIA  COLLEGE  OF  PHARMACY 

EDITED  BY 

HENRY  KRAEMER 

— *M   jxxM^T 

PUBLICATION  COMMITTEE  FOR  1914 

SAMUEL  P.  SADTLER  M.  I.  WILBERT 

JOSEPH  W.  ENGLAND  CHARLES  H.  LaWALL 

JOSEPH  P.  REMINGTON  JOHN  K.  THUM 

AND  THE  EDITOR 


VOLUME  86 


PHILADELPHIA 
1914 


THE  AMEEIOAN 


JOURNAL  OF  PHARMACY 


JANUARY,  1Q14 


THE  ASSAY  OF  MERCURIC  CHLORID  TABLETS. 

^^^_^B/Robert  M.  Chapin, 
Bureau  of  AmmaTlndustry,  U.  S.  Department  of  Agriculture. 

At  the  present  time  mercuric  chlorid  tablets,  especially  those 
prepared  after  the  well-known  Wilson  formula,  are  very  widely 
used,  and  are  used  moreover  with  implicit  confidence  in  the  accuracy 
of  their  declared  content  of  mercuric  chlorid  under  circumstances 
whic*h  render  such  accuracy  a  matter  of  considerable  importance  to 
individual  welfare  and  to  the  public  health  in  general.  There  can 
be  no  question  of  the  desirability  of  assay  methods  which  shall  be 
fairly  accurate,  yet  simple  and  rapid  enough  to  be  freely  used  by 
manufacturers,  pharmacists,  hospitals,  and  sanitary  officials  at  a 
minimum  of  expense  and  chemical  equipment. 

Several  years  ago  Rupp  1  proposed  a  rapid  method  for  the  deter- 
mination of  mercury  in  various  compounds,  involving  the  following 
steps :  ( 1 )  Reduction  to  metallic  mercury  by  formaldehyde  in  alkaline 
solution  in  presence  of  potassium  iodid ;  (2)  solution  of  the  precipi- 
tated mercury  in  excess  of  standard  iodin  solution  after  acidification 
with  acetic  acid ;  and  (3)  titration  of  excess  iodin  by  standard  sodium 
thiosulphate.  A  modification  of  the  method  is  now  official  in  the 
German  Pharmacopoeia  for  the  assay  of  tablets  composed  of  mer- 
curic and  sodium  chlorids. 

In  this  country  Smith  2  has  thoroughly  studied  the  Rupp  method 
when  applied  to  pure  mercuric  chlorid,.  obtaining,  when  certain  modi- 

1  Rupp,  E.  Ueber  die  volumetrische  Bestimmung  des  Quecksilbers.  Be- 
richte  der  Deutschen  Chemischcn  Gesellschaft,  Vol.  39,  No.  14,  pp.  3702-3704. 
Berlin,  Nov.  10,  1906. 

2  Smith,  Carl  E.  Volumetric  determination  of  mercury.  American 
Journal  of  Pharmacy,  Vol.  83,  No.  7,  pp.  311-315.    Phila.,  July,  191 1. 

(1) 


2 


Mercuric  Chi  or  id  Tablets. 


f  Am.  Jour.  Pharm. 
\    January,  1914. 


fications  were  introduced,  a  recovery  of  99.8  to  100.3  Per  cent-  of  the 
mercuric  chlorid  employed.  Smith's  modifications  involved  (1) 
the  use  of  a  larger  amount  of  substance  and  reagents  to 
reduce  experimental  errors,  (2)  a  longer  time  of  action  by 
formaldehyde  to  insure  complete  reduction  to  metallic  mercury, 
and  (3)  a  much  less  degree  of  acidification  before  addition  of  iodin, 
since  large  amounts  of  free  acetic  acid  tend  to  produce  low  results. 
Smith  states  that  similarly  good  quantitative  results  were  obtained 
when  the  method  was  applied  to  mixtures  of  mercuric  chlorid  and 
ammonium  chlorid  colored  with  aniline  dyes.  That  is,  the  modified 
method  is  implied  to  be  applicable  to  commercial  tablets  prepared 
after  Wilson's  formula  (mercuric  chlorid,  7.3  grains;  ammonium 
chlorid,  7.7  grains;  coloring  matter,  q.s.). 

In  this  laboratory  Smith's  statements  and  results  were  con- 
firmed on  solutions  of  pure  mercuric  chlorid.  Utter  failure,  however, 
followed  attempts  to  apply  his  method  either  to  commercial  tablets  or 
to  similar  laboratory  mixtures  of  mercuric  and  ammonium  chlorids. 
Abnormal  precipitates  appeared  after  addition  of  iodin,  and  results 
obtained  were  erratic  and  much  too  low.  At  the  same  time  the  method 
given  in  the  German  Pharmacopoeia,  slightly  modified,  was  found 
to  work  smoothly  and  quantitatively. 

The  addition  of  formaldehyde  to  a  solution  of  ammonium  salts 
produces  hexamethylenamin,  which  is  known  to  form  difficultly  solu- 
ble compounds  with  both  iodin  and  mercuric  salts.3  In  Smith's 
modification,  then,  conditions  appear  to  be  such  as  to  permit  the 
formation  and  separation  of  hexamethylenamin  compounds  to  the 
resultant  vitiation  of  the  process,  while  in  the  method  of  the  German 
Pharmacopoeia  the  greater  dilution  at  which  the  process  is  worked 
either  inhibits  the  formation  of  such  interfering  substances,  or,  more 
probably,  is  sufficient  to  retain  them  in  solution  and  hence  in  a  harm- 
less condition.  At  all  events,  if,  in  addition  to  other  minor  modifi- 
cations later  to  be  noted,  a  volume  of  75  c.c.  of  water  is  added  at 
the  time  the  contents  of  the  flask  are  acidified  before  the  addition  of 
iodin,  no  abnormalities  appear  in  the  working  of  Smith's  process, 
and  the  results  are  equally  accurate  in  the  presence  or  absence  of 
ammonium  chlorid. 

Inasmuch  as  the  method  finally  chosen  here  as  most  satisfactory  is 

3  Cohn,  G.  Die  Verbindung  des  Urotropins.  Pharmazeutische  Zentral- 
halle,  Vol.  52,  No.  44,  pp.  1173-1179.    Dresden,  Nov.  2,  191 1. 


Am.  Jour,  pharm.  |  Mercuric  Chlorid  Tablets. 

January,  1914.  j 


3 


somewhat  different  in  details  from  either  of  the  two  modifications 
already  noted,  the  points  of  difference  and  the  reasons  therefor  will 
be  discussed. 

In  the  first  place,  while  it  is  true  that  the  use  of  large  amounts 
of  substance  and  reagents  tends  to  reduce  the  relative  magnitude  of 
experimental  errors,  there  is  a  point  beyond  which  any  slight  possible 
gain  in  accuracy  is  attained  only  at  the  sacrifice  of  an  unwarranted 
measure  of  simplicity,  convenience,  and  rapidity.  It  is  certainly  open 
to  question  whether  this  point  is  not  passed  by  Smith's  modification 
with  its  considerable  consumption  of  standardized  solutions,  espe- 
cially when  the  total  volume  of  liquid  worked  with  is  increased  by 
the  75  c.c.  of  water  here  found  necessary  to  prevent  interference  by 
hexamethylenamin  compounds.  The  writer  therefore  recommends 
the  employment  of  0.20  to  0.25  gram  of  mercuric  chlorid  for  each  test, 
and  the  addition  of  25  c.c.  of  tenth-normal  iodin. 

Experiment  1. — To  test  the  limits  within  which  the  results  of  parallel 
determinations  may  fall  if  the  above  proportions  are  used,  a  series  of  seven 
parallel  tests  were  made  on  a  solution  of  commercial  tablets,  using  the  equiva- 
lent of  one-half  tablet  for  each  test.  Aside  from  the  use  of  volumetric 
apparatus  which  had  passed  the  requirements  of  the  Bureau  of  Standards,  no 
precautions  not  employed  in  ordinary  quantitative  work  in  any  laboratory 
were  observed.  The  cubic  centimetres  of  iodin  solution  (tenth-normal  X 
0.978)  consumed  in  the  solution  of  mercury  were  as  follows:  (1)  17.72; 
(2)  17.73;  (3)  17.68;  (4)  17.69;  (5)  17.72;  (6)  17.73;  (7)  17-65;  an  extreme 
difference  of  0.08  c.c.  The  average  weight  of  mercuric  chlorid  per  tablet  was 
therefore  found  to  be  from  0.4677  to  0.4698,  a  difference  of  0.45  per  cent. 
The  range  of  variation  reported  by  Smith  in  a  series  of  five  tests  by  his 
method  on  pure  mercuric  chlorid  was  0.5  per  cent. 

Secondly,  the  proportion  of  potassium  iodid  should  be  consider- 
ably increased  over  that  employed  by  either  Rupp  or  Smith  in  order 
to  avoid  the  formation  of  mercurammonium  compounds  which  result 
when  caustic  alkali  in  excess  is  added  to  a  solution  containing  potas- 
sium mercuric  iodid  and  ammonium  salts,  as  in  the  well-known 
"  Nessler  test." 

Thirdly,  the  presence  of  ammonium  salts  in  one  way  or  another 
operates  to  retard  the  reduction  to  metallic  mercury  so  that  it  is  not 
complete  in  5  minutes  though  apparently  so  after  10  minutes. 

Lastly,  commercial  formaldehyde  solutions  often  contain  foreign 
substances,  some  of  which  conceivably  may  consume  iodin,  and  in 
fact  such  solutions  have  here  been  found  which  did  possess  this 


4 


Mercuric  Chlorid  Tablets.  \ A™-  Jour-  ftj*- 

l    January,  1914. 


power  in  slight  but  distinct  degree.  Hence  a  standard  thiosulphate 
solution  should  be  made  the  basal  standard  against  which  the  iodin 
solution  is  standardized  by  running  a  blank  assay  with  the  other 
solutions  and  reagents  intended  for  actual  use. 

The  method  finally  chosen  for  tablets  after  Wilson's  formula  is 
as  follows :  Weigh  5  tablets,  dissolve  in  water,  dilute  to  100  c.c,  and 
pass  through  a  dry  filter,  discarding  the  first  20  c.c.  of  filtrate.  From 
the  remainder  pipette  10  c.c.  (equivalent  to  one-half  tablet)  into  a 
glass-stoppered  250  c.c.  Erlenmeyer  flask,  add  2l/2  grams  pure  pow- 
dered potassium  iodid,  mix  to  entirely  dissolve,  and  then  wash 
down  the  sides  of  the  flask  with  20  c.c.  of  normal  caustic  alkali. 
Add  exactly  3  c.c.  of  37  per  cent,  formaldehyde  solution,  mix 
thoroughly,  and  let  stand  for  at  least  ten  minutes,  swirling  the 
flask  occasionally.  Then  wash  down  the  sides  of  the  flask  with 
a  mixture  of  5  c.c.  of  36  per  cent,  acetic  acid  with  25  c.c.  water;  mix, 
and  without  delay  run  in  from  a  burette  25  c.c.  of  tenth-normal 
iodin  while  constantly  swirling  the  flask.  Stopper  the  flask  tightly, 
shake  vigorously  for  three  minutes,  then  after  giving  the  contents  a 
final  swirling  motion  leave  at  rest  for  two  minutes.  If  then  no  undis- 
solved mercury  can  be  detected  at  the  bottom  the  stopper  is  removed, 
rinsed,  together  with  the  neck  of  the  flask,  with  a  stream  from  a 
wash-bottle,  and  the  excess  iodin  titrated  with  tenth-normal  sodium 
thiosulphate,  adding  starch  solution  only  when  the  iodin  is  nearly 
consumed. 

Standardize  the  iodin  solution  by  running  a  blank  assay  on  10  c.c. 
distilled  water. 

Subtract  the  volume  of  thiosulphate  solution  used  in  the  assay 
from  that  used  in  the  blank.  The  difference  multiplied  by  the  factor 
0.0271  for  strictly  tenth-normal  sodium  thiosulphate  will  give  the 
average  weight  of  mercuric  chlorid  per  tablet.  For  a  direct  check 
upon  the  value  of  the  sodium  thiosulphate  solution  run  an  assay  on 
10  c.c.  of  a  2.y2  per  cent,  solution  of  mercuric  chlorid  of  known 
purity. 

While  mercuric  chlorid  is  the  important  active  ingredient  of  tab- 
lets made  according  to  Wilson's  formula,  nevertheless  ammonium 
chlorid  is  an  essential  part  of  the  formula,  added  in  order  to  render 
the  tablets  easily  soluble  and  to  inhibit  the  formation  of  insoluble, 
and  hence  inactive,  compounds  of  mercury.   An  assay  of  such  tablets 


Am.  jour,  pharm.  \  Mercuric  Chlorid  Tablets.  5 

January,  1914.    j  ^ 

ought  therefor  to  include  an  estimation  of  ammonium  chlorid,  espe- 
cially when  a  simple  and  convenient  method  is  available. 

The  method  for  ammonium  chlorid  here  adopted  is  an  adaptation 
of  the  process  of  Ronchese,4  which  is  based  on  the  reaction  between 
formaldehyde  and  a  neutral  ammonium  salt,  whereby  methylenamin, 
(CH2)fiN4,  is  formed,  the  acid  originally  contained  in  the  ammo- 
nium salt  being  released  and  becoming  titratable  with  standard 
caustic  alkali  and  phenolphthalein.  The  strengths  of  reagents,  etc., 
recommended  by  Wilkie  5  have  been  adopted. 

Titration  by  standard  alkali  and  phenolphthalein  can  not  of 
course  be  conducted  in  presence  of  mercuric  chlorid.  This  difficulty, 
however,  is  easily  overcome  by  throwing  the  mercury  into  a  complex 
ion  through  the  addition  of  potassium  iodid.  The  method  is  as  fol- 
lows:  Into  each  of  two  150  c.c.  Erlenmeyer  flasks  pipette  5  c.c.  (one- 
fourth  tablet)  of  the  tablet  solution  previously  prepared  for  the  esti- 
mation of  mercuric  chlorid  (5  tablets  per  100  c.c.)  and  add  to  each 
flask  2  c.c.  of  a  20  per  cent,  solution  of  potassium  iodid. 

Dilute  one  volume  of  37  per  cent,  formaldehyde  solution  with 
three  volumes  of  water,  measure  20  c.c.  of  the  mixture  into  a  small 
flask,  add  0.5  c.c.  of  phenolphthalein  indicator  solution,  neutralize 
with  tenth-normal  barium  hydrate  or  caustic  alkali,  then  flow  the 
solution  over  the  sides  of  one  of  the  flasks  (flask  A)  containing  tablet 
solution,  and  mix  well.  To  the  other  flask  (flask  B)  containing  tablet 
solution  add  about  65  c.c.  water. 

Now  add  to  flask  A  25  c.c.  water  and  titrate  with  tenth-normal 
barium  hydrate  or  tenth-normal  caustic  alkali  free  from  carbon 
dioxid  until,  by  using  flask  B  as  a  standard  for  comparison,  a  color 
change  is  perceptible  (titration  A). 

Add  methyl  red  to  flask  B  and  titrate  with  either  tenth-normal 
acid  or  alkali  as  needed  (titration  B). 

To  titration  A  add  titration  B  if  performed  with  acid,  or  subtract 
if  performed  with  alkali.  The  resultant  figure  multiplied  by  the 
factor  0-.0214  for  strictly  tenth-normal  alkali  will  give  the  average 
weight  of  ammonium  chlorid  per  tablet. 

4  Ronchese,  A.  Nouveau  procede  de  dosage  de  rammoniaque.  Journ.  de 
Pharmacie  et  de  Chimie,  Vol.  25,  No.  12,  pp.  611-617.    Paris,  June  16,  1907. 

5  Wilkie,  John  M.  The  Ronchese  method  of  determining  ammonia  and 
its  extension  to  the  determination  of  the  total  acid  content  of  organic  am- 
monium salts  and  ammoniacal  solutions.  Journal  of  the  Society  of  Chemical 
Industry,  Vol.  29,  No.  1,  pp.  6-7.   London,  Jan.  15,  1910. 


6  Mercuric  Chlorid  Tablets.  {Aj^™£  PmT' 

For  a  direct  check  upon  the  value  of  the  tenth-normal  alkali  run 
an  assay  upon  5  c.c.  of  a  2]/2  per  cent,  solution  of  pure  ammonium 
chlorid. 

Solutions,  reagents,  and  water  used  should  be  free  from  carbon 
dioxid. 

Ordinarily  titration  B  is  very  small,  sometimes  zero,  but  usually 
calling  for  the  addition  of  a  few  drops  of  tenth-normal  acid. 

As  respects  the  end  points  with  the  indicators  it  is  only  possible 
to  state  that  up  to  the  present  time  no  blue  or  green  tablets  which 
have  been  received  by  the  writer  have  presented  the  slightest  difficulty. 
The  characteristic  colors  of  the  indicators  of  course  do  not  appear  in 
the  presence  of  other  coloring  matter,  but  the  change  of  tint,  if 
standards  of  comparison  are  used,  is  delicate  and  distinct.  No  red 
tablets  have  been  received  for  examination. 

The  reliability  of  the  method  may  be  shown  by  noting  a  few 
results. 

Experiment  2. — Four  tests  made  on  5  c.c.  of  a  solution  of  2  grams  each 
of  commercial  CP.  chlorids  of  mercury  and  ammonium  per  100  c.c.  gave  the 
following  figures  for  titration  A  (titration  B  —  O),  made  with  barium  hydrate 
solution  (tenth-normal  X  1.021)  which  had  been  standardized  against  a  labora- 
tory stock  solution  of  half-normal  hydrochloric  acid:  (1)  18.24  c.c;  (2)  18.26 
c.c;  (3)  18.29  cc-'>  (4)  18.26  c.c;  an  extreme  difference  of  0.05  c.c.  and  a 
recovery  of  99.6  to  99.9  per  cent,  of  the  ammonium  chlorid  employed. 

Experiment  3. — Three  titrations  made  on  5  c.c.  of  the  solution  of  commer- 
cial tablets  employed  in  Experiment  1  gave  titration  B  as  zero,  and  titration 
A  as  (1)  22.64  c.c;  (2)  22.58  c.c;  (3)  22.62  c.c;  an  extreme  difference  of 
0.06  c.c 

It  appears,  therefore,  that  assay  methods  are  now  available  for 
accurately  and  conveniently  estimating  mercuric  and  ammonium 
chlorid  in  commercial  tablets.  Knowing  the  weight  of  tablets  taken 
to  prepare  the  stock  solution  for  assay,  estimation  of  coloring  matter 
and  "  filler  "  is  merely  a  matter  of  subtraction.  Further  possible 
tests,  such  as  degree  of  solubility,  amount  of  insoluble  matter,  and 
uniformity  of  weight  of  individual  tablets,  are  a  matter  of  discretion 
with  the  analyst  and  need  no  discussion. 


A  January  m™'  \  Resistance  of  Guinea  Pigs  to  Poisonini 


SEASONAL   VARIATIONS    IN    THE    RESISTANCE  OF 
GUINEA  PIGS  TO  POISONING  BY  OUABAIN  AND  BY 
liquid'  PREPARATIONS  OF  DIGITALIS. 

By  C.  C.  Haskell,  A.B,  M.D. 

In  a  previous  paper  1  it  has  been  shown  that  guinea  pigs  are  more 
resistant  to  poisoning  by  ouabain  during  certain  months  of  the  year 
than  at  others.  These  results  were  confirmed  in  a  general  way  by 
Vanderkleed  and  Pittenger  2  in  a  subsequent  publication.  It  is  of 
interest  to  compare  the  results  secured  in  this  laboratory  with  those 
reported  by  Vanderkleed  and  Pittenger. 

I  have  used  male  pigs  exclusively,  and  have  been  compelled  to 
employ  animals  differing  largely  in  weight;  the  majority,  however, 
weighed  250  grams  or  more,  so  it  seems  best  to  compare  my  results 
with  those  obtained  by  Vanderkleed  and  Pittenger  using  "  large 
males."  In  order  to  facilitate  comparison,  the  average  minimum 
lethal  dose  has  been  expressed  in  fractions  of  a  gram  per  gram  body 
weight  and  put  in  the  following  tabular  form : 

Table  I. 


Month. 

Vanderkleed  and  Pittenger. 

Haskell. 

January  

.  1912 

.OOOOOO25 

.OOOOOO52  + 

February  

1912 

. OOOOOO30 

.OOOOOO37 

March.  

. . 1912 

.OOOOOO32 

. OOOOOO36 

April  

1912 

. OOOOOO33 

. OOOOOO4O 

May  

1912 

. OOOOOO33 

. OOOOOO45 

June  

1912 

. OOOOOO33 

. OOOOOO4O 

July  

.  .1911 

. 0000002 I 

August  

1911 

. 0000002 1 

. OOOOOO29 

September  

. . 191 1 

. 0000002 I 

. OOOOOO30 

October  

1911 

. 0000002 1 

. OOOOOO36 

November  

1911 

. OOOOOO24 

. OOOOOO52 

December  

1911 

.OOOOOO28 

.OOOOOO52 

It  is  readily  seen  that  the  same  general  conclusion  is  deducible 
from  both  series  of  tests  :  the  resistance  of  the  pigs  is  least  during  the 
hot  summer  months  and  greatest  in  the  cooler  weather.  In  August, 
there  is  a  difference  of  38  per  cent,  between  the  lethal  dose  required 

1  Am.  Jour.  Pharm.,  Vol.  84,  No.  6,  p.  241,  1912. 

2  Jour.  Am.  Ph.  Assoc.,  Vol  n,  No.  5,  P-  558,  1913- 


8  Resistance  of  Guinea  Pigs  to  Poisoning  {^^"J 


Pharm 
1914. 


in  Indianapolis  and  that  determined  in  Philadelphia ;  and  in  January, 
the  enormous  preponderance  of  108  per  cent,  is  shown  by  the  In- 
dianapolis lethal  dose.  Obviously,  it  is  scarcely  to  be  expected  that 
we  should  secure  very  closely  comparable  results  in  assaying  a  galeni- 
cal if  such  divergence  occurs  in  testing  a  "  pure  principle." 

In  endeavoring  to  account  for  this  disagreement,  the  technic  em- 
ployed should  be  closely  scrutinized.  It  is  a  well-recognized  fact 
that  testing  digitalis  upon  frogs  requires  the  closest  attention  to 
details  and  necessitates  the  avoidance  of  any  disturbing  factors  such 
as  large  variations  in  the  weight  of  the  animals  and,  especially,  ex- 
tremes of  temperature.  From  previous  statements  of  those  who 
have  employed  the  guinea  pig  method,  one  is  led  to  infer  that  such 
extreme  caution  is  not  necessary  when  this  method  is  used,  and  the 
results  of  Vanderkleed  and  Pittenger  seem  to  show  that  weight  and 
age  are  factors  of  little  moment. 

In  all  of  my  experiments,  a  solution  of  ouabain,  I  to  10,000  in  25. 
per  cent,  alcohol,  was  used.  Vanderkleed  and  Pittenger  do  not  state 
whether  alcohol  was  present  in  the  solutions  they  employed,  but  its 
absence  would  explain  the  smaller  dose  determined  by  them  as 
compared  to  the  dose  I  found  necessary  in  August,  because  alcohol 
exerts  a  similar  antagonistic  action  toward  the  absorption  of  subcu- 
taneously-administered  ouabain  as  it  does  toward  digitalis  adminis- 
tered in  this  way.  Some  other  explanation,  however,  is  necessary  to 
account  for  the  difference  between  the  minimum  lethal  dose  deter- 
mined in  Indianapolis  in  January  (.00000052  -(-)  and  that  determined 
in  Philadelphia  for  the  same  month  (.00000025).  The  pigs  used  by 
Vanderkleed  and  Pittenger  were  kept  in  fairly  warm  quarters ;  while 
our  animals  were  subjected  to  considerable  variations  in  temperature, 
the  thermometer  occasionally  registering  as  low  as  500  F.  This,  I 
believe,  has  an  important  bearing  on  the  resistance  of  the  guinea  pigs 
and,  together  with  the  influence  of  the  alcohol  used  in  my  experi- 
ments, may  serve  to  explain  the  difference  in  the  lethal  dose  as 
determined  in  the  winter  months. 

Since  this  earlier  report,  the  minimum  lethal  dose  of  ouabain 
in  25  per  cent,  alcohol  has  been  determined  upon  guinea  pigs  in  a 
number  of  different  months  and  a  comparison  is  of  some  interest. 
In  Table  II  such  a  comparison  is  given. 

These  figures  indicate  that  the  temperature  influences  the  powers 
of  resistance.    During  the  extremely  cold  winter  of  1911-12  the 


*  January  ^iST'  }  Resistance  of  Guinea  Pigs  to  Poisoning.  9 

dose  for  November,  r^.  fiber,  and  January  was  .00000052:  while 
during  the  much  milder  winter  of  191 2-1 3,  the  lethal  dose  was 
smaller.  Where  comparison  is  possible  in  other  months,  the  differ- 
ence never  amounts'  to  more  than  15  per  cent. 


Table  II. 


Month. 


January. . . 
February. . 

March  

April  

May  

June  

July  

August  

September 
October. . . 
November. 
December. 


IOII. 


.  00000029 
00000030 
, 00000036 
, 00000052 
. 00000052 


1912. 


, 00000052  + 
.00000037 
, 00000036 
. 00000040 
. 00000045 
. 00000040 


.00000036 
. 00000042 
. 00000040 
. 00000045 


00000040 
00000042 

.00000037 
. 00000045 

.00000025 
.00000025 


Seasonal  variations  in  the  resistance  of  test  animals  may  be 
obviated  by  the  use  of  a  satisfactory  standard,  and  Vanderkleed  and 
Pittenger  suggest  the  use  of  ouabain  when  galenicals  of  the  "  heart 
tonic  "  group  are  tested  upon  guinea  pigs.  The  use  of  ouabain  is 
justified,  however,  only  when  it  has  been  shown  that  the  variations 
in  the  resistance  toward  poisoning  by  ouabain  parallels  that  toward 
poisoning  by  the  galenicals  under  consideration.  Opportunity  has 
occurred  to  determine  the  minimum  lethal  dose  of  a  small  number 
of  samples  of  tincture  and  fluid  extract  of  digitalis  at  different  seasons 
of  the  year.  Some  of  the  tinctures  were  made  by  the  U.S. P.  method 
and  some  were  made  with  a  menstruum  containing  75  per  cent,  alco- 
hol. All  of  the  fluid  extracts  were  made  with  a  menstruum  contain- 
ing 70  per  cent,  or  80  per  cent,  alcohol. 

In  testing  the  tinctures,  portions  were  evaporated  to  a  semi- 
solid consistence  upon  the  water-bath  and  the  residue  suspended  in 
an  amount  of  distilled  water  equal  to  the  original  volume  of  the 
portion  taken  for  evaporation.  The  same  procedure  was  followed 
with  the  fluid  extracts,  save  that  the  volume  of  distilled  water  was 
five  times  that  of  the  fluid  extract  taken.  For  reasons  that  will  be 
apparent  later;  it  is  desirable  that  the  preparations  be  divided  into 
two  groups ;  one  comprising  preparations  containing  about  50  per 


io  Resistance  of  Guinea  Pigs  to  Po«onitt^.jAJj™J  llTI.™' 

cent,  alcohol ;  the  other  comprising  those  containing  from  70  to  80 
per  cent,  alcohol. 

The  comparison  of  the  lethal  doses  for  two  tinctures  made  with 
50  per  cent,  alcohol  and  the  lethal  dose  for  ouabain  during  the  same 
months  is  given  in  Table  III.  N 


Table  III. 


June,  1912. 

Oct.,  1912. 

Dec,  1912. 

Jan.,  1913. 

Aug.,  1913. 

Ouabain  

Tr.  Digitalis  U.  S.  P. 

434900  

Tr.  Digitalis  U.  S.  P. 

457579  

. OOOOOO4 
.004 

. OOOOOO42 
.004 

. OOOOOO45 
.007  + 
.0075 

. OOOOOO4 
.OO65 

.00000025 

.OO42 

.0052 

So  far  as  can  be  judged  by  this  limited  number  of  experiments, 
"  seasonal  "  variations  in  the  resistance  of  guinea  pigs  toward  poison- 
ing by  ouabain  and  by  tinctures  of  digitalis  made  with  50  per  cent, 
alcohol  follow  the  same  general  curve.  In  January,  1913,  the  lethal 
dose  for  Tincture  434900  was  .0065,  while  in  July,  1913,  it  showed  a 
decrease  of  35.4  per  cent.:  the  lethal  dose  of  ouabain  showed  a 
decrease  of  37.5  per  cent,  during  the  same  time.  In  December,  1912, 
the  dose  of  Tincture  457579  was  .0075,  while  in  July,  191 3,  it  was 
30.6  per  cent,  less:  the  dose  of  ouabain  suffered  a  decrease  of  44 
per  cent. 

In  testing  the  preparations  containing  relatively  high  percentages 
of  alcohol,  entirely  different  results  were  obtained.  These  are  so 
surprising  that  it  was  only  after  confirming  them  repeatedly  that  I 
could  feel  that  they  were  not  due  to  some  error  in  testing.  The  tests 
were  carried  out  in  a  manner  exactly  similar  to  those  dealing  with 
the  tinctures  just  discussed  and  the  difference  in  the  behavior  seems 
to  depend  upon  an  essential  difference  in  the  composition  of  prepara- 
tions made  with  50  and  75  per  cent,  alcohol  respectively. 

From  these  results,  it  is  evident  that  no  seasonal  variation  has 
been  observed  in  the  resistance  of  guinea  pigs  to  poisoning  by  fluid 
preparations  of  digitalis  made  by  percolation  of  the  leaf  with  men- 
strua containing  70  to  80  per  cent,  alcohol.  Tinctures  made  with 
75  per  cent,  alcohol  differ  in  several  important  points  from  those 
made  with  50  per  cent,  alcohol,  but  it  seems  almost  incredible  that 
the  resistance  of  guinea  pigs  to  poisoning  by  the  two  should  follow 


Am.  Jour.  Tharm.  } 
January,  1914.  j 


M  agma 


B ism  ut hi. 


1 1 


Table  IV. 


Ouabain1 

Tr.  Digi- 
talis 
471124 

Tr.  Digi- 
talis 
46 10 1 1 

Tr.  Digi- 
talis 
467056 

Tr.  Digi- 
talis2 
24678 

F.  E.  Digi- 
talis 
461015 

F.  E.  Digi- 
talis 
1654092 

Jan.  1912 

1913 
Feb.  1912 

1913 
Mar.  1912 

1913 
Apr.  1912 

1913 
May  1912 

1913 
June  1912 

1913 
July  1912 

1913 
Aug.  19 1 2 

1913 
Sept.  1912 

1913 
Oct.  1912 

1913 
Nov.  1912 

52 
40 

37 
42 

36 

.OO24 

.0025 
.0025 

.OO27 

40 
37 
45 
45 
40 

25 
29 
25 

42 
40 

45 

.0030 

.0025 

.0025 
.0025 

.00022 

.OOO47 

.0025 

.0020 

.OO23 

.OOO23 

.OOO32 

1913 
Dec.  1912 

1913 

.0022 

1  The  figures  in  this  column  represent  fractions  of  a  gram  to  the  eighth  decimal 

(.00000052). 

2  Alcohol  not  removed  from  this  tincture. 


such  different  lines.  A  confirmation  of  these  observations  would  cer- 
tainly suggest  that  careful  pharmacological  study  of  digitalis  prepara- 
tions made  with  different  menstrua  would  not  entail  a  waste  of  time. 
From  the  Laboratory  of  Experimental  Medicine,  Eli  Lilly  and 
Company,  Indianapolis,  Aug.  26,  1913. 


MAGMA  BISMUTHI. 

By  S.  Bertha  Muller,  P.D., 
Assistant  Pharmacist  at  the  German  Hospital,  Philadelphia. 

In  recent  years  Magma  Bismuth  has  become  quite  popular,  so 
much  so  that  it  was  deemed  advisable  to  make  the  preparation 
official. 

With  that  end  in  view  several  formulas  have  been  proposed  and 
duly  tried  out,  but  in  our  experience  have  not  proved  generally 
satisfactory. 


12 


Magma  Bismuthi. 


IAm.  Jour.  Pharm. 
j    January,  1914. 


The  formulas  proposed  direct  ammonia  water  to  be  used  to  pre- 
cipitate the  bismuth  nitrate.  This,  in  our  experience,  leads  to  con- 
siderable trouble  trying-  to  wash  the  resulting  Magma  free  from  the 
excess  of  ammonia.  It  takes  a  great  deal  of  water  to  do  so  and  even 
if  one  has  succeeded  in  getting  the  final  washings  to  no  longer  react 
with  phenolphthalein  the  Magma  itself  will  always  give  a  strong 
reaction.  To  reduce  the  amount  of  ammonia  water  leads  to  a  reaction 
in  the  opposite  direction,  giving  a  decided  acid  reaction  which  causes 
the  gradual  solution  of  the  bismuth  hydroxide.  Furthermore,  when 
the  Magma  is  poured  on  a  strainer  for  the  purpose  of  washing  it, 
the  surface  of  the  Magma  very  soon  develops  a  metallic  coating 
which  certainly  points  to  a  decomposition  going  on  and  may  be  due 
to  exposure  to  air.  Unfortunately  this  is  the  only  way  the  Magma 
can  be  washed  because  distilled  water  has  the  property  of  causing 
the  Magma  to  curdle  into  large  flaky  masses,  taking  up  considerable 
water  and  holding  it  so  that  it  is  utterly  impossible  to  get  the  Magma 
to  settle  in  order  to  wash  it  by  decantation,  thus  preventing  undue 
exposure  to  air. 

Attention  should  also  be  drawn  to  the  fact  that  the  amount  of 
bismuth  subnitrate  used,  results  in  too  thick  a  Magma.  Further- 
more, 80  grams  of  bismuth  subnitrate  cannot  be  satisfactorily  dis- 
solved in  60  c.c.  of  nitric  acid.  It  takes  i  c.c.  of  nitric  acid  for  every 
gram  of  bismuth  subnitrate  to  be  dissolved. 

However,  with  some  modifications  the  proposed  official  formula 
will  give  satisfactory  results.  In  the  first  place  the  amount  of 
bismuth  should  be  somewhat  reduced,  then  ammonium  carbonate 
should  be  substituted  for  ammonia  water,  and  lastly,  distilled  water 
containing  i-iooo  sodium  chloride  should  be  used.  By  using  am- 
monium carbonate  the  resulting  Magma  is  not  nearly  so  alkaline,  it 
will  not  react  with  phenolphthalein  but  will  and  should  react  alkaline 
toward  methyl  orange.  It  therefore  does  not  require  nearly  so  much 
washing.  It  only  needs  to  be  washed  until  it  is  practically  tasteless. 
The  use  of  this  small  amount  of  sodium  chloride  in  distilled  water 
prevents  the  curdling  of  the  Magma,  and  it  therefore  can  readily  be 
washed  by  decantation,  no  strainer  being  required.  After  sufficient 
washing  it  is  allowed  to  settle  to  the  required  volume,  which  usually 
takes  about  a  week. 

Spigot  water  can  also  be  used  in  place  of  distilled  water  if  it  has 
been  previously  boiled  with  i  per  cent,  magnesium  carbonate  for 


Aj;,mTry/i9i4m"}       Books  as  a  Source  of  Disease.  13 

about  15  minutes,  then  cooled  and  filtered  and  1-1000  sodium  chloride 
added. 

The  following  formula  has  been  fairly  satisfactory : 

Bismuth  Subnitrate    50.0 

Nitric  Acid   50.0 

Ammonium  Carbonate    80.0 

Distilled  water  to  make   1000.0 

Dilute  the  nitric  acid  with  an  equal  volume  of  water  and  dissolve 
the  bismuth  subnitrate  in  it,  dilute  further  to  300  c.c.  and  filter 
through  cotton. 

Dissolve  the  ammonium  carbonate  in  3000  c.c.  distilled  water 
containing  1-1000  sodium  chloride  and  filter. 

Pour  the  acid  solution  slowly  and  with  constant  stirring  into 
the  alkaline  solution.  When  the  resulting  precipitate  has  subsided, 
decant  the  supernatent  liquor  and  wash  by  decantation  until  the 
Magma  is  practically  tasteless,  using  distilled  water  containing 
1-1000  sodium  chloride.    Then  allow  to  settle  to  1000  c.c. 

When  tested  the  Magma  should  react  alkaline  toward  methyl 
orange. 

BOOKS  AS  A  SOURCE  OF  DISEASE. 

By  William  R.  Reinick. 

I  do  not  for  a  moment  want  anyone  to  think  that  I  am  endeavor- 
ing to  prove  that  books,  as  fomites,  are  so  dangerous  that  they 
should  be  shunned  like  the  plague,  but  simply  to  show  that  books, 
especially  when  greasy  or  moist  fingers  are  placed  upon  the  pages 
and  covers,  are  excellent  hiding  grounds  for  bacteria,  both  pathogenic 
and  non-pathogenic,  and  that  the  same  care  should  be  used  as  in 
handling  other  objects  of  like  character. 

Is  Such  Transmission  Possible? 

As  far  as  our  exact  knowledge  of  books  and  papers  as  a  source 
of  danger  is  concerned,  we,  at  the  present  time,  have  very  little 
evidence,  but  what  we  have  proves  beyond  question,  that  disease  may 
be  contracted  by  this  means.  ( )n  the  other  hand  there  are  many 
reputable  physicians  who  claim  that  transmission  by  this  means  is 
an  impossibility,  due  to  the  fact  that  the  organisms  could  not  exist 


14 


Books  as  a  Source  of  Disease. 


<  Am.  Jour.  Pharm. 
(    January,  1914. 


for  any  length  of  time  under  such  adverse  conditions.  A  statement 
of  this  character  is  generally  made  by  one  who  only  has  a  superficial 
knowledge  of  the  subject,  especially  in  its  biological  aspect.  The 
apparatus  needed  to  properly  conduct  experiments  upon  bacteria 
is  quite  expensive,  and  generally,  the  young  physician  who  has  just 
graduated  has  the  time  and  possesses  the  enthusiasm  to  undertake 
these  researches,  but  not  the  capital,  and  then  when  he  has  the 
means,  he  has  so  many  patients  that  he  cannot  spare  the  time. 

Another  trouble  is  the  extreme  difficulty  which  arises  when  one 
is  prepared  to  study  this  subject.  On  account  of  the  great  surface 
covered  by  the  pages  of  the  books,  it  means  a  long  and  tedious  series 
of  experiments,  and  even  then,  on  account  of  their  being  invisible  to 
the  eye,  one  is  not  sure  that  he  has  obtained  every  speck  of  life  that 
may  be  on  the  paper. 

The  knowledge  that  we  are  now  acquiring  as  to  the  great  resist- 
ance of  these  small  forms  of  life  to  adverse  conditions  of  climate 
and  atmosphere,  their  resistance  to  degrees  of  heat,  their  wonderful 
adaptability  to  rapid  changes  of  environment,  food,  and  their  power 
to  remain  dormant  for  a  period  more  or  less  unknown  at  the  present 
day,  their  ability  to  form  a  protective  coat,  which  prevents  pene- 
tration when  placed  in  material  that  would  otherwise  destroy  them, 
all  these  points  indicate  that  we  may  be  on  the  wrong  track  in  using 
the  present  means  of  eradication.  And  furthermore,  in  making  our 
laboratory  tests  we  are  forced  to  isolate  the  colonies,  giving  conditions 
foreign  to  their  natural  state  of  existence,  and  also  the  difficulty  in 
separating  them  into  distinct  species. 

Newman  states  as  follows :  "  A  word  may  be  said  here  respecting 
the  much-discussed  question  of  species  of  Bacteria.  A  species 
may  be  defined  as  '  a  group  of  individuals,'  which,  however  many 
characters  they  share  with  other  individuals,  agree  in  presenting  one 
or  more  characters  of  a  peculiar  and  hereditary  kind  with  some  cer- 
tain degree  of  distinctness.  Now,  as  regards  bacteria,  there  is  no 
doubt  that  separate  species  occur  and  tend  to  remain  as  separate 
species.  It  is  true,  there  are  many  variations,  due  in  large  measure 
to  the  medium  in  which  the  organisms  are  growing — variations  of 
age,  adaptation,  nutrition,  etc. —  yet  the  different  species  tend  to 
remain  distinct.  Involution  forms  occur  frequently,  and  degenera- 
tion invariably  modifies  the  normal  appearance.  But  because  of  the 
occurrence  of  these,  morphological  and  even  pathological  differences 
of  environment  and  physical  conditions  must  have  marked  effect 


Am.  Jour.  Pharm.  ) 
January,  1914.  j 


Books  as  a  Source  -  of  Disease. 


15 


upon  such  sensitive  units  of  protoplasm  as  bacteria ;  it  has  recently 
been  proven  that  one  great  reason  why  modification  occurs  in  pure 
artificial  culture  is  that  the  species  has  been  isolated  from  amongst 
its  colleagues  and  doomed  to  a  separate  existence.  One  of  the  most 
abstruse  problems  in  the  immediate  future  of  the  science  of  bacteri- 
ology is  to  learn  what  intrinsic  characters  there  are  in  species  or 
individuals  which  act  as  a  basis  for  the  association  of  organisms  for 
a  specific  purpose.  Some  bacteria  appear  to  be  unable  to  perform 
their  regular  function  without  the  aid  of  others.  An  example  of 
such  association  is  well  illustrated  in  the  case  of  tetanus,  for  it  has 
been  shown  that  if  the  bacilli  and  spores  of  tetanus  alone  obtain  en- 
trance to  a  wound,  the  disease  may  not  follow  the  same  course  as 
when  with  the  specific  organism  of  lactic  acid  bacilli,  or  the  common 
organisms  of  suppuration  or  putrefaction  also  gain  entrance.  Again, 
the  virulence  of  other'bacteria  is  also  increased  by  means  of  associa- 
tion. The  bacilli  coli  is  an  example,  for,  in  conjunction  with  other 
organisms,  this  bacilli,  although  normally  present  in  health  in  the 
alimentary  canal,  is  able  to  set  up  acute  intestinal  irritation,  and 
various  changes  in  the  body  of  an  inflammatory  nature." 

Among  the  higher  forms  of  life  we  have,  in  a  few  hundred  of 
years,  recognized  natural  changes,  or  often  brought  the  change  about 
by  artificial  selection.  Now  if  a  change,  quite  noticeable,  can  be 
made  during  a  period  of  years,  in  forms  which  do  not  produce  more 
than  one  or  two  generations  a  year,  what  changes  are  able  to  take 
place,  in  forms  capable  of  producing  a  new  generation  every  twenty 
or  thirty  minutes,  and  these  changes  invisible  to  us? 

Another  source  of  failure  to  obtain  positive  results  is  due  to  the 
fact  that  conclusions  are  generally  arrived  at  from  twenty-four 
hour  tests ;  and,  if  there  is  no  result  within  that  period,  the  experi- 
ment is  marked  negative  and  the  material  destroyed. 

Very  little  information  of  value,  to  help  in  deciding  whether  or 
not  books  act  as  carriers,  was  received  from  the  various  Boards  of 
Health  of  the  United  States.  A  circular  letter  requesting  a  list  of 
cases,  the  source  of  which  was  traced  to  books  and  papers,  was 
sent  to  the  Boards  of  Health  of  each  State  and  forty-one  cities. 
Answers  were  received  from  only  ten  States  and  nineteen  cities, 
about  30  per  cent,  of  the  total  number  of  letters  sent. 

With  these  replies  no  cases  were  given,  although  some  of  the 
officials  stated  it  to  be  their  belief  that  diseases  were  contracted 
through  contact  with  books,  while  others  ridiculed  such  a  possibility. 


16  Books  as  a  Source  of  Disease.       { ATanuiry  191T' 

Quite  a  number  of  physicians  have  sent  me  histories  of  cases,  which 
they  have  observed  during  their  practice. 

The  medical  and  library  periodicals  are  constantly  printing 
notices  about  disease  being  contracted  from  books,  and  as  in  the 
case  of  the  theory  of  insects  transmitting  disease  germs,  at  first 
ridiculed,  but  now  acknowledged  to  be  true  by  the  most  skeptical, 
so  are  books  now  passing  through  the  same  criticism. 

Diseases  Claimed  to  Have  Been  Traced  to  Books. 

Scarlet  Fever. — Dr.  J.  Allen  Palmer,  of  Erie,  Kansas,  notes  a 
case  of  scarlatina  developing  in  a  girl,  living  in  a  town  where  there 
had  been  no  cases  of  the  disease  for  months,  nor  had  she  been 
exposed  to  personal  contact.  Investigation  showed  that  the  patient 
had  received  a  letter  a  few  days  previous  to  the  appearance  of  the 
rash,  from  a  child  living  some  sixty  miles  from  her,  who  was  just 
recovering  from  scarlatina.  Another  case  of  transmission  was  traced 
by  Dr.  Howard  W.  Lyon,  of  Chicago.  In  this  instance  a  little  girl 
living  in  Chicago  contracted  scarlatina  from  being  allowed  to  handle 
a  letter  just  received  from  a  home  in  Minneapolis,  where  one  of  the 
family  had  the  disease. 

Dr.  A.  Maverick,  of  San  Antonio,  Texas,  sent  the  following  case : 
A  boy  convalescent  from  scarlet  fever  read  a  book  from  the  public 
library  and  used  as  book-marks  strips  of  skin  peeled  from  his  hands 
and  feet.  Unknown  to  the  physician,  the  book  was  returned  to  the 
library  by  a  servant  of  the  household  with  no  attempt  at  sterilization 
or  even  removing  the  pieces  of  skin.  During  the  next  month,  two 
boys  in  different  families  who  borrowed  the  book  from  the  library, 
caught  scarlet  fever  and  one  died  from  the  disease. 

Diphtheria. — Dr.  Robert  Britton,  of  Downsville,  New  York, 
writes  of  two  cases  in  1902,  one  of  the  patients  dying,  and  as  there 
were  no  cases  of  the  disease  in  the  neighborhood,  the  question  arose 
where  had  the  children  contracted  the  infection.  Questioning  re- 
vealed, that  on  account  of  the  weather  and  conditions  of  the  road 
they  did  not  attend  school  on  March  27,  but  played  in  a  house 
having  a  garret,  in  which  were  stored  some  old  school  books  which 
had  been  taken  from  an  old  farm-house  on  this  farm — in  which  in 
i860  had  occurred  six  cases  of  diphtheria,  four  of  which  were  fatal 
in  forty-eight  hours. 

Small-pox. — Small-pox  is  one  of  the  most  contagious  diseases, 
and  few  who  are  exposed  escape  infection.   The  contagion  exists  in 


Am.  jour,  pharm.  >       Books  as  a  Source  af  Disease.  17 

January,  1(J14.    J  '  / 

the  pustules,  in  the  fluid  of  the  body,  and  apparently  in  the  ex- 
halation from  the  lungsand  skin.  The  dried  scales  thrown  off  during 
desquamation  are  the  most  important  element  in  disseminating  the 
malady,  and  is  often  communicated,  through  the  medium  of  clothes, 
furniture,  books,  etc.,  which  have  come  in  contact  with  patients. 

Dr.  P.  A.  Jordan,  of  San  Jose,  California,  states  the  following: 
A  man,  a  great  reader,  continuously  used  books  from  a  circulating 
library  located  in  a  neighboring  town  in  which  there  was  an  epidemic 
of  small-pox,  and  later  developed  a  severe  form  of  small-pox. 

Blood-Poisoning. — Dr.  Emericus  Karacson,  while  making  a  trans- 
lation of  a  Turkish  Manuscript,  in  one  of  the  Mosques  in  Turkey, 
had  his  fingers  soiled  with  some  of  the  mould  which  covered  the  old 
musty  tomes,  and  accidentally  touched  a  cut  on  his  face ;  a  few  weeks 
later  his  face  swelled  up,  causing  him  intense  pain.  A  quick  opera- 
tion relieved  him  of  this  and  his  face  regained  its  normal  size,  and 
he  soon  resumed  his  work,  apparently  in  perfect  health.  About  a 
month  later  he  was  taken  ill  with  fever  and  treated  first  for  influenza, 
then  for  typhoid  fever.  His  condition  growing  worse,  a  Hungarian 
physician  was  sent  for,  who  diagnosed  the  case  at  once  as  blood- 
poisoning,  caused  no  doubt  by  the  fungi  that  had  entered  the  patient's 
system  through  the  abrasion  on  the  face,  and  he  died  within  a  few 
days. 

Venereal  Diseases. — That  the  danger  to  man  from  what  are  called 
the  "  social  evil  "  diseases,  after  exacting  a  cost  in  human  life  and 
physical  disability  beyond  computation,  and  the  necessity  of  using 
means  which  will  prevent  its  spread,  is  now  recognized,  as  seen  by 
the  numerous  societies  being  formed  to  furnish  speakers  and  publish 
literature  upon  the  subject,  thus  forcing  the  public  to  face  the  question 
as  it  has  never  been  done  before. 

A  list  of  articles  found  to  be  carriers  of  the  germs  of  gonorrhea, 
the  one  most  likely  to  be  contracted  through  contact,  would  include 
every  article  of  domestic  and  public  use,  and  even  the  hands  of  the 
unclean  and  ignorant  may  transfer  the  germs  to  the  articles.  A  num- 
ber of  cases  have  been  traced  to  books. 

Diseases,  besides  these  mentioned,  have  been  named  as  being 
transmitted  by  books,  and  there  is  no  reason  to  doubt  that  the  germs 
of  other  diseases  found  on  fomites  will  also  be  found  on  books. 
The  bacillus  of  anthrax,  which  occurs  in  cattle,  must  certainly  be 
found  on  the  leather  bindings,  as  it  is  frequently  transmitted  through 


?8 


Books  as  a  Source  of  Disease. 


(Am.  Jour.  Pharm. 
\    January,  1914. 


abrasions  of  the  hands  in  cases  of  those  who  have  the  occasion  to 
handle  infected  wools  and  hides. 

Tuberculosis. — The  number  of  bacilli  in  the  sputum  of  a  person 
suffering  from  tuberculosis  is  enormous.  Nuttall  estimated  that  a 
person  moderately  advanced  in  the  disease,  expectorated  between  two 
and  four  billions  of  bacilli  every  twenty-four  hours.  One  having  this 
disease  does  not  at  once  become  helpless,  and  in  the  meantime  the 
patient  generally  spends  a  great  deal  of  his  spare  time  reading,  and 
as  this  disease  usually  causes  the  one  inflicted  to  cough  a  great  deal, 
often  involuntarily,  it  is  but  natural  that  particles  of  the  sputum  will 
be  caught  on  the  paper  of  the  books,  ready  to  be  transmitted  to 
another  victim. 

Dust. — I  do  not  think  that  enough  study  has  been  given  to  the 
bacteria  found  in  dust,  as  far  as  public  institutions  are  concerned. 
Careful  consideration  of  the  examinations  already  made  of  dust  from 
various  sources,  especially  in  the  industrial  trades  during  the  past 
few  years,  will  show  at  once  that  the  health  is  often  affected  by  the 
impurities  found  in  the  air  inhaled,  and  that  the  purifying  of  this 
air  is  of  greatest  importance  from  a  sanitary  standpoint.  Besides  the 
danger  from  exposure  to  the  so-called  diseases,  the  germs  of 
which  are  stated  to  be  borne  in  the  air,  the  pollution  of  the  air  by 
organic  and  inorganic  dust  is  beyond  a  doubt  the  cause  of  a  great 
deal  of  ill-health,  and  death. 

An  analysis  made  by  Prof.  Charles  H.  Lawall  of  dust  collected  by 
me  at  the  State  Library  of  Florida,  at  Tallahasse,  off  of  books  that 
had  not  been  disturbed  for  many  years,  gave  the  following  result: 

"  Ash  (inorganic  material,  mainly  sand),  54.90  per  cent. 

"  Organic  matter  consists  of  much  unidentifiable  matter,  in  which, 
however,  could  be  distinguished  microscopically  the  following :  wood 
fragments,  cotton,  linen,  silk,  wool  (some  of  them  dyed  bright 
colors),  hairs  of  various  kinds,  both  plant  and  animal,  starch  grains, 
spore  and  an  occasional  yeast  cell.  No  evidence  was  found  of 
arsenic  or  mercury  or  other  poisonous  metals  or  their  compounds, 
except  what  might  be  called  a  faint  trace  of  arsenic,  which  was  traced 
by  a  method  so  delicate  as  to  detect  arsenic  in  almost  any  substance 
from  which  it  has  not  been  specifically  removed." 

Dr.  McFadden  and  Mr.  Lunt  seem  to  prove  the  paucity  of 
bacteria  in  very  dusty  air.  The  evidence  otherwise  available  is 
entirely  conclusive  that  the  risk  to  disease  infection  is  much  greater 
indoors  than  out  in  the  open,  where  the  germs  are  exposed  to  the 


Am.  Jour.  Pharm.  1  Books  dS  d  Source  Off  Disease.  IQ 

sunlight,  which  is  a  great  factor  in  keeping  the  germs  in  an  inactive 
state.  '  j 

But,  besides  the  danger  of  infection  from  inhaling  disease  germs 
found  in  the  dust,  there  is  also  to  be  considered  that  it  is  the  cutting 
edges  of  the  particles  of  dust,  which  when  inhaled  scratch  or  cut  the 
delicate  air  passages  leading  to  the  lungs  and  also  the  lungs  them- 
selves. The  finer  dust  will  not,  perhaps,  act  as  quickly  as  the  coarser 
grains,  but  it  means  that  the  evil  result  will  take  a  much  longer  time 
before  making  its  appearance. 

It  is  known  that  those  who  spend  most  of  their  time  in  outdoor 
occupations,  generally  have  better  health  than  those  who  are  com- 
pelled to  work  in  factories,  offices,  etc.,  and  the  first  thought  of  sani- 
tary science  to-day  is  the  elimination  of  dust. 

It  is  extremely  difficult,  in  fact  almost  impossible,  to  trace  many 
cases  of  infection  on  account  of  the  long  period  between  the  first 
infection  and  the  appearance  of  the  disease  in  a  form  to  demand 
medical  attention. 

Dr.  Hugh  H.  Brown,  of  Washington,  D.  C,  and  an  assistant,  in 
1907,  moved  a  large  number  of  books  which  had  not  been  disturbed 
for  quite  some  time.  Within  a  few  days  both  contracted  severe  colds, 
characterized  by  distinct  bubbling,  and  a  severe  cough  accompanied 
by  a  feeling  of  compression  and  pain  in  the  chest,  and  an  exceed- 
ingly profuse  and  purulent  expectoration  of  a  deep  yellow  color  the 
consistency  of  thick  cream.   The  cold  lasted  about  two  weeks. 

Vitality  of  Bacteria. — Before  considering  the  mode  of  overcom- 
ing these  organisms,  consideration  should  first  be  given  to  their 
power  of  resistance  to  disinfection,  sterilization,  etc. 

Bacteria  exist  in  nature  in  three  states : 

( 1)  As  adult  or  fully-developed  and  active  microorganisms,  with 
all  the  characteristics  of  parasites. 

(2)  As  spores  or  reproductive  cells  endowed  with  latent  life. 

(3)  As  desiccated  germs,  whose  vital  principle  had  been  sus- 
pended but  not  destroyed ;  which,  when  placed  in  a  moist  and  suitable 
environment,  possess  the  power  of  resuscitation. 

"  The  air  germs,"  says  Professor  Tyndall,  "  differ  much  among 
themselves  in  their  tendency  to  development ;  there  are  some  which 
are  young  and  there  are  others  which  are  old,  some  dry  and  some  wet. 
The  same  water  infected  by  those  germs  requires  more  or  less  time 
to  develop  bacterial  activity.  This  explains  the  difference  in  the 
rapidity  with  which  epidemic  diseases  act  upon  different  persons. 


20 


Books  as  a  Source  of  Disease. 


/Am.  Jour.  Pharm. 
I    January,  1914. 


In  certain  cases  the  period  of  incubation,  if  it  can  be  so  called,  is  long-, 
in  others  it  is  short;  the  difference  is  the  result  of  the  different 
degrees  of  preparedness  of  the  contagious  matter,  and  I  personally 
believe  that  the  health  of  the  person  infected  has  most  to  do  with  the 
appearance  or  non-appearance  of  a  disease." 

The  length  of  time  that  the  different  pathogenic  bacteria  can 
withstand  drying  varies  greatly.  Krausz  placed  bacteria  from  48- 
hour  old  cultures  in  books  and  kept  them  in  the  dark  at  room  tem- 
perature. He  found  that  cholera  lived  only  40-95  days  and  tubercle 
bacilli  80-103  days.  Other  investigations  confirm  his  results  except 
in  the  cases  of  tuberculosis  and  diphtheria.  Abel  found  that  diph- 
theria bacilli  retained  their  virulency  on  toys  for  six  months  and 
this  is  the  length  of  time  that  Von  Scham  gives.  Lion  and  Von 
Schab  both  say  that  tubercle  bacilli  withstand  drying  from  six  to 
nine  months. 

The  number  of  bacteria  that  may  be  found  on  much-used  books 
was  investigated  by  Lion.  A  novel  from  a  public  library  varied  from 
250  .bacteria  per  100  square  centimetres  on  the  middle  of  a  clean 
page  to  1,250,  1,875,  and  3,350  on  the  dirty  edges.  A  college  atlas 
showed  from  650  to  1,075  Per  100  square  centimetres;  an  anatomy 
book  2,275  to  3,700.  The  bindings  were  by  far  the  richest  in  bacteria, 
yielding  on  an  average  of  7,550  per  square  centimetre. 

As  to  the  pathogenic  bacteria  that  may  occur  on  books,  the  follow- 
ing investigations  are  of  great  interest.  Krausz  inoculated  seven 
guinea  pigs  with  dirty  pieces  of  paper  from  much-used  books  and 
they  all  died  of  peritonitis.  The  eighteen  inoculated  with  pieces  from 
clean  books  remained  healthy.  Du  Cazal  and  Catrin  found  Staphy- 
lococcus pyogenes  on  an  old  book  in  a  hospital.  Most  striking  of  all 
are  Mitelescu's  experiments.  He  took  60  much-used  books  that  had 
been  in  a  public  library  from  six  months  to  two  years ;  he  cut  out  the 
dirtiest  parts,  soaked  them  in  salt  solution,  centrifuged  the  liquid 
and  inoculated  guinea  pigs  with  the  sediment.  Nineteen  died  of 
septicemia,  and  twelve  of  streptococcus  infection.  He  repeated  the 
experiment  with  thirty-seven  books  from  three  to  six  years  old. 
Fourteen  of  the  guinea  pigs  died  of  septicemia,  and  fifteen  contracted 
tuberculosis.  The  damp  dirt  on  the  older  books  was  a  good  medium 
for  tubercle  bacilli. 

The  following  abstracts  are  taken  from  the  report  made  to  the 
Board  of  Trustees  of  the  Chicago  Public  Library  upon  books  in  that 


Aj»1mair,,Pi'il4m'J       Boohs  as  a  Source  of  Disease.  21 

• 

library  by  Dr.  W.  A.  Kuflewski  and  are  of  value  as  showing  the 
germs  to  be  found  on  books  long  in  use. 

These  books  were  selected  by  Mr.  F.  H.  Hild,  Librarian,  and 
Dr.  Reynolds,  the  object  being  to  get  the  books  that  were  most  worn 
and  most  soiled,  and  the  examination  was  made  by  Dr.  Adolph 
Gehrmann,  who  reported  as  follows : 

D  2017a    From  delivery  station,  14  years. 

19       Cultures  from  page  57,  brown  spot — negative. 

Cultures  from  torn  places  on  cover.  <' 

(A)  Staphylococci  and  saprophytes. 

(B)  Negative. 

C  7357      Delivery  station,  20  years. 

Cultures  from  title  page — negative. 

Cultures  from  title  page — negative. 

Cultures  from  page  19 — negative. 

Cultures  from  page  19 — negative. 

H  2455c    Delivery  station,  6  years. 

Cultures  from  top  of  page  278 — negative. 
Cultures  from  leather  back — Staphylococcus  pyogenes  albus. 
Cultures  from  bottom  edge  of  pages — Staphylococcus  pyogenes 
albus. 

Cultures  from  top  edge  of  pages — saprophytes  and  S.  pyogenes. 

F  8346c    Circulating  department,  2  years:  Popular  juvenile. 
Cultures  from  leather  back — negative. 
Cultures  from  top  of  pages — negative. 
Cultures  from  page  190 — negative. 

F  494aa     Circulating  department,  26  years  :  Popular  fiction. 
Cultures  from  spot  on  page  25 — negative. 
Culture  from  leather  back — negative. 
Cultures  from  bottom  pages — negative. 

RR  281     Buck's  Cyclopaedia,  14  years  :  Reference  book. 

Cultures  from  leather  back—  1  colony  of  Staphylococci. 
Cultures  from  edge  of  cover — 1  colony  of  Staphylococci. 
Cultures  from  dirty  page — Staphylococci. 
Cultures  from  clean  pages — Staphylococci. 

Summary  of  Results. 
Negative  results :  3  books — C  735 ;  58  346c ;  and  E  494aa. 

Cultures  from  covers  showing  Staphylococci:  3  books — D  2017a,  H  2455c,  and 

281. 
1 

Cultures  from  pages  showing  Staphylococci:  2  books — H  2455c  and  RR281. 

I 


22  Books  as  a  Source  of  Disease.        { A m™" 

A  series  of  cultures  from  the  hands  of  two  persons  in  the  labora- 
tory were  made  in  the  same  manner  and  these  showed  a  few  colonies 
of  saprophytes  and  Staphylococci  pyogenes  albus.  In  a  general 
way  these  cultures  were  similar  to  those  giving  positive  results  made 
from  the  books. 

The  method  employed  in  making  these  cultures  was  to  take  a  few 
drops  of  sterile  bouillon  and  with  a  platinum  wire  rub  it  upon  the 
place  from  which  the  inoculations  were  made  and  then  transfer  this 
loop  of  bouillon  to  the  blood  serum  boxes  used  by  the  department 
for  diagnosis  of  diphtheria.  These  were  placed  in  an  incubating 
oven  for  forty-eight  hours.  The  resulting  colonies  were  examined 
microscopically. 

Control  cultures  were  made  on  several  boxes  by  first  placing  the 
drop  of  bouillon  on  the  sterile  slide  and  then  transferring  it  to  the 
blood  serum  media. 

In  none  of  the  cultures  were  diphtheria  bacilli  found.  The 
Staphylococcus  pyogenes  albus  is  one  of  the  pus  bacteria  usually 
found  upon  the  skin  of  most  individuals.  The  saprophytes  are 
accidental  non-pathogenic  bacteria  from  the  air,  and  are  of  no 
consequence. 

Dr.  Kuflewski  states  that  "  after  personal  investigation  and  ex- 
amination of  three  sets  of  books  taken  at  random  from  the  shelves 
of  the  Chicago  Public  Library  I  am  prepared  to  state  that  I  found 
bacteria  in  large  numbers  in  all  the  samples  and  that  each  book 
was  more  or  less  infected.  These  bacteria  were  in  large  numbers 
and  were  both  pathogenic  and  non-pathogenic— the  word  pathogenic 
meaning  '  disease-producing.'  " 

In  many  instances  these  bacteria  do  not  harm,  not  even  the 
pathogenic,  because  of  the  resistance  of  the  tissue — being  unimpaired 
— or  because  of  the  comparatively  small  numbers  of  bacteria  which 
gain  access  to  the  tissues ;  but  under  favorable  circumstances,  such 
as  a  simple  exposure  to  cold  and  especially  to  bronchitis,  which  is  so 
prevalent  in  Chicago,  a  little  wound  or  an  abrasion  of  the  surface 
of  the  body,  a  little  scratch  of  the  mucous  membrane  or  of  the 
skin-,  which  as  we  all  know  is  often  treated  as  insignificant  and  is 
neglected,  may  be  the  means  of  introduction  into  the  system  of  the 
most  infectious  disease  germs.  It  is  well  known  that  a  fresh  wound 
absorbs  bacteria  and  their  toxins  very  rapidly. 

I  have  had  in  my  own  experience  a  case  in  which  I  satisfactorily 
proved  that  a  child  contracted  an  infectious  disease  in  the  eye,  from 


Aja/wy  ^914"'}       Books  as  ct  Source  af  Disease.  23 

the  page  of  a  book.  Prof.  Dr.  W.  A.  Evans,  who  is  an  authority, 
states  the  case  of  a  person  who  was  infected  with  typhoid  germs  from 
books,  which  case  was  established  beyond  question.  I  had  another 
case  two  or  three  years  ago ;  a  gentleman  who  was  suffering  from 
cancer  in  the  roof  of  the  mouth,  in  which  the  tongue  and  lips  were 
also  affected,  was  reading  books  from  public  libraries  in  this  city 
for  nearly  two  years  and  until  I  was  called  to  treat  him.  He  had 
been  treated  before  by  the  "  faith  cures  "  and  by  the  followers  of 
Dowie.  This  patient  was  found  expectorating  minute  pieces  of  his 
tongue  and  lips,  which  were  a  cancerous  tissue,  all  over  the  pages 
of  the  book  he  read.  That  they  were  cancerous  was  not  only  proven 
by  my  own  examination,  but  by  that  of  Dr.  LeCount,  an  eminent 
bacteriologist,  who  reported  to  me  that  the  piece  of  tissue  submitted 
was  cancerous,  containing'  cancerous  cells. 

Of  course  I  prohibited  this  person  from  reading  any  more  books 
from  the  libraries,  and  told  his  wife  to  be  very  careful  as  the  disease 
was  contagious. 

In  my  own  experiments  I  had  no  difficulty  in  obtaining  colonies 
from  the  pages  and  bindings  of  all  of  the  books  examined,  and  I  also 
obtained  cultures  of  various  forms  from  dust  many  years  old,  which 
according  to  the  text-books,  should  have  been  destroyed. 

Flies. — These  insects  are  now  known  to  carry  germs.  In  some 
cases  as  many  as  six  million  have  been  found  on  a  single  specimen. 
In  very  few  cases  are  libraries  protected  by  screens ;  the  fly  just  from 
a  patient  suffering  from  a  contagious  disease,  or  off  the  waste  matter 
in  a  near-by  cesspool,  has  easy  access  to  the  interior  of  the  library, 
where,  alighting  upon  a  binding  or  page  of  an  open  book  it  proceeds 
to  eject  a  number  of  germs  with  its  excreta,  or  by  rubbing  its  body 
with  its  forelegs,  shakes  large  numbers  orf,  which  find  ready  lodge- 
ment, especially  if  the  spot  where  the  rubbing  takes  place  is  greasy, 
as  is  generally  the  case  where  a  book  has  been  much  used  or  circu- 
lated for  quite  a  number  of  times. 

People  do  not  seem  able  to  overcome  the  vulgar  habit  of  moisten- 
ing the  fingers  in  turning  over  the  leaves  of  the  books  and  again  plac- 
ing the  finger  on  the  lips  each  time  to  remoisten,  never  considering 
that  each  time  he  is,  perhaps,  transferring  germs  to  fertile  soil  for 
propagation,  resulting  in  sickness  later  on,  or  in  case  of  a  patient 
already  suffering  from  disease,  especially  tuberculosis,  helping  to 
inflict  another  victim  with  the  disease.    And  we  all  know  that  sick 


24 


Books  as  a  Source  of  Disease. 


i  Am.  Jour.  Pharm. 
\    January,  1914. 


persons,  especially  in  the  convalescent  stage,  spend  a  great  deal 
of  their  time  in  reading  books  and  magazines. 

Disinfection. — This  process  in  killing  germs  in  books,  although 
recommended,  especially  by  those  who  have  the  disinfectants  and  the 
apparatus  for  sale,  may  be  dismissed  as  of  very  little  use,  on  account 
of  the  impossibility  of  the  gases  penetrating  into  the  interior  of  the 
volumes,  and  in  no  case,  even  if  the  entire  surface  is  reached,  will 
they  remove  all  of  the  spores. 

Sterilisation. — Both  steam  and  hot  air  sterilization  are  of  little 
value  for  books,  because  the  first  will  cause  the  paper  of  the  books 
to  absorb  the  moisture,  swell  and  deform  the  book,  and  while  in  the 
case  of  hot  air  sterilization,  the  heat  would,  by  drying  up  all  the 
moisture  in  the  books,  have  the  same  effect,  besides,  in  the  case  of 
books  bound  with  leather,  cause  the  leather  to  stretch  and  often 
break. 

The  heat  also  will  absorb  the  moisture  and  the  paper  will  become 
dry  and  brittle,  lessening  the  life  of  the  volume.  At  present  I  do 
not  believe,  that  there  is  any  method  which  may  be  depended  upon 
to  entirely  eliminate  the  possibility  of  diseases  being  contracted 
through  contact  with  fomites,  such  as  books  and  the  hundreds  of 
other  articles  in  daily  use,  constantly  being  transferred  to  a  sick- 
room, returned  and  ready  for  another  victim.  I  believe  that  some 
of  the  State  Boards  of  Health  are  now  beginning  to  recognize  the 
futility  of  quarantining  and  disinfecting.  Instead  they  are  spending 
all  their  energies  in  improving  sanitary  conditions  as  to  the  necessity 
of  cleanliness  and  the  proper  care  of  health.  If  a  person  using  books 
or  any  other  of  the  numerous  articles  named  as  conveying  germs  will 
use  precautions  as  to  the  degree  of  cleanliness  of  the  article  they 
handle,  and  will  take  the  proper  care  of  their  health,  they  need  have 
no  fear  of  contracting  any  disease  by  means  of  a  book  or  any  other 
article. 

Suppose  that  a  library  did  disinfect  their  books,  what  claim  can 
they  make  that  the  book  has  no  germs,  after  it  has  been  placed  on  a 
shelf  next  to  another  book  or  been  handled  by  a  reader  or  one  of  the 
assistants.  Dr.  A.  W.  Doty,  of  New  York  City,  states  along  the  line 
of  using  disinfectants  at  intervals,  "  I  know  of  nothing  in  public 
sanitation  which  is  more  farcical  than  the  general  or  periodical  dis- 
infection of  books  with  gaseous  disinfectants  for  the  purpose  of 
preventing  infection.  These  agents  have  no  penetration  of  any 
account,  and  I  have  little  faith  in  them  for  this  purpose.    I  believe 


Am.  Jour.  Pharm. ) 
January,  1914.  / 


Ehrlich's  Chemotherapy. 


25 


that  the  careful  dusting  of  the  books  and  an  abundance  of  fresh  air 
and  proper  ventilation  in  a  library  is  all  that  need  be  done  under 
ordinary  conditions." 

He  here  touches  the  remedy,  cleanliness,  in  relation  to  the  books, 
but  the  same  care  that  should  be  given  to  keeping  the  books  clean 
should  also  be  insisted  upon  for  the  employees  and  readers  of  libraries 
and  all  places  where  dust  may  accumulate. 

A  visit  to  almost  any  library  will  generally  show,  by  placing  the 
hands  in  back  of  the  books  upon  the  shelves,  that  there  is  a  great  deal 
of  dust  lying  there.  Very  few  libraries,  even  those  recently  erected, 
have  had  the  vacuum  system,  which  seems  to  be  almost  perfected, 
installed.  Instead  of  making  the  reader  wash  his  or  her  hands  before 
using  a  book,  it  is  very  difficult  for  one  to  obtain  access  to  the  lava- 
tory to  wash  his  hands  even  if  he  so  desires.  In  fact,  there  are  some 
libraries  which  have  no  lavatories  at  all  for  the  public. 

Books  are  often  placed  on  shelves  in  stacks,  poorly  ventilated  and 
lighted.  The  results  obtained  in  the  library  at  Hawaii,  whose  books 
were  constantly  being  destroyed  by  insects  while  stored  in  a  dark, 
badly  ventilated  building,  but  was  almost  eliminated  when  transferred 
to  a  well-lighted  and  ventilated  building,  prove  the  value  of  pure  air 
and  sunlight.  Not  disinfectant  plants,  but  sunlight,  fresh  air,  the 
elimination  of  dust,  and  the  proper  cleanliness  on  the  part  of  the 
employees  and  readers,  is  the  way,  not  only  to  prevent  books  from 
becoming  fomites,  but  also  the  people  becoming  carriers  in  this  age 
of  prevention. 


EHRLICH'S  CHEMOTHERAPY.1 

How  His  Logical,  Systematic  Campaign  Against  Certain 
Diseases  Has  Demonstrated  the  Value  of  Scientific 
Methods  in  Therapeutical  Problems. 

By  Henry  P.  Talbot. 

Chemotherapy  has  been  called  "  a  new  science.''  It  should, 
rather,  be  regarded  as  the  designation  of  a  scientific  field  in  which 
therapeutics  and  chemistry  intermingle  in  the  solution  of  problems 
involving  the  principles  of  both  of  the  older  sciences,  much  as  do 
physics  and  chemistry  in  so-called  "  physical  chemistry/'  which  is 
not,  on  that  account,  regarded  as  a  "  new  "  science. 

1  Reprinted  from  Science  Conspectus,  March,  1913. 


26 


Ehrlich's  Chemotherapy. 


(  Am.  Jour.  Pharm. 
I    January,  1914. 


Therapeutics  is  defined  as  that  branch  of  medical  science  "  which 
deals  with  the  composition,  application,  and  modes  of  operation  of 
the  remedies  for  disease."  But  it  has  now  taken  on  a  somewhat 
broader,  though  less  exact,  meaning,  and  is  understood  to  include 
the  general  administration  of  medicine,  questions  of  hygiene  and 
dietetics,  and  much  that  has  to  do  mainly  with  the  general  well- 
being  of  the  individual.  That  chemistry  must  be,  as  it  has  been  for 
centuries,  inseparable  from  the  study  of  therapeutics  is  obvious, 
and  the  advance  from  the  simplicity  of  the  theory  of  Geber,  accord- 
ing to  which  the  animal  organism  was  made  up  of  only  "  sulphur  " 
and  "  mercury  "  to  our  still  very  imperfect  knowledge  of  the  com- 
plex changes  of  physiological  processes  is,  indeed,  remarkable.  But 
modern  medical  and  chemical  science  is  not  content  with  the  mere 
alleviation  of  the  ravages  of  existing  disease,  that  is,  with  the  modify- 
ing or  assisting  of  functions  temporarily  disturbed,  but  has  struck 
more  directly  at  the  root  of  the  trouble  by  devising  means  actually  to 
destroy  the  causative  agents  and  thus  arrest  the  disease,  or  to  render 
the  animal  organism  inhospitable  to  these  causative  agents,  as,  for 
example,  through  the  anti-toxins  and  the  methods  of  preventive 
medicine  in  general. 

All  this  had  been  done  even  before  the  advent  of  chemotherapy. 
What,  then,  is  new  about  this  combination  of  scientific  effort  in  two  al- 
lied fields  ?  Essentially  this  :  It  is  a  logical,  systematic  campaign  against 
diseases  which  are  caused  by  the  infection  of  the  animal  organism 
by  parasites  (i.e,  bacteria  or  protozoa)  by  means  of  chemicals  which 
have  not  been  found  by  empirical  and  more  or  less  haphazard 
methods,  but  have  been  synthesized  and  built  up  solely  for  the  pur- 
pose in  hand,  and  as  the  result  of  researches  which  have  called  for 
the  highest  type  of  accurate  observation  and  analytical  reasoning 
for  their  execution.  In  this  way  it  has  been  found  possible  to  devise 
means  by  which  the  animal  organism  can  be  sterilized  with  respect 
to  the  parasites  in  question,  and  the  consequent  symptoms  of  disease 
can  be  arrested. 

The  development  of  this  field  is  due  almost  entirely  to  Professor 
Paul  Ehrlich,  of  Frankfort,  and  his  co-workers.  Dr.  Ehrlich  was 
educated  as  a  physician,  but  has  now  become  also  one  of  the  most 
accomplished  and  able  investigators  in  the  field  of  synthetic  organic 
chemistry.  A  conception  of  the  significance  of  his  work  can,  perhaps, 
be  best  obtained  by  noting  important  phases  in  its  progressive  de- 
velopment. 


A  January  Pi9i4m* }  Eltrlich's  Chemotherapy.  27 

More  than  thirty  years  ago  Ehrlich  began  using  coal-tar  colors  in 
his  physiological  studies,  employing  them  as  stains  for  preparations 
to  be  examined  under  the  miscroscope.  It  is,  of  course,  now  com- 
monly known  that  certain  dye-stuffs  appear  to  have  a  selective 
affinity  for  certain  tissues  of  the  body,  or  for  certain  parasites  when 
residing  within  it,  and  these  stains  are  in  every  day  use  by  the 
pathologist.  But  it  was  not  so  thirty  years  ago,  and  Ehrlich  first 
found  that  a  dye-stuff  known  as  methylene-blue,  and  its  congeners, 
were  the  only  colors  which  would  stain  live  nerve  tissue,  and  drew 
from  this  the  important  inference,  which  is  at  the  basis  of  chemo- 
therapy, that  this  was  because  of  a  particular  receptivity  for  these 
dye-stuffs  on  the  part  of  these  tissues  or  parasites.  It  is  easy  to 
understand  something  of  the  importance  of  this  use  of  these  stains, 
or  dyes,  if  it  is  recalled  that  the  changes  produced  in  the  individual 
cells  or  tissues  by  drugs  are  not  detectable  even  under  the  micro- 
scope in  most  cases,  and  that  it  is  only  through  these  stains  that  a 
knowledge  of  what  has  actually  happened  can  be  even  approximately 
learned. 

Ehrlich  concluded  from  his  observations  that  it  was  probable  that, 
since  these  tissues  and  parasites  possessed  this  receptivity  for  these 
specific  bodies,  there  must  be  some  definite  effect  produced  as  a  re- 
sult of  the  combination,  if  combination  it  were,  and  proceeded  to 
conduct  investigations  in  this  direction.  After  some  time  these 
researches  were  rewarded,  and  in  1890  Ehrlich  and  Lappmann  pub- 
lished a  paper  on  the  pain-relieving  properties  of  methylene-blue, 
and,  later,  Ehrlich  and  Guttmann  found  that  the  same  dye  was  fatal 
to  one  type  of  the  plasmodium,  the  parasite  which  causes  malaria. 
As  the  latter  field  of  investigation,  that  of  the  effect  upon  parasites, 
appeared  very  promising,  they  turned  their  attention  to  a  particular 
class  of  parasites  known  as  trypanosomes,  because  these  could  be 
more  easily  studied  by  the  inoculation  of  mice. 

The  disease-producing  parasites  are  sometimes  of  vegetable 
origin,  as  the  bacteria,  and  sometimes  of  animal  nature,  as  the  pro- 
tozoa. The  trypanosomes  are  worm-like  bodies,  somewhat  larger 
than  bacteria,  belonging  to  the  animal  class,  and  the  diseases  which 
they  produce  prevail  most  generally  in  tropical  countries.  Of  these 
diseases,  surra,  most  generally  known  in  India  among  cattle,  dogs 
and  camels;  nagana  (tsetse-fly  disease),  known  in  Africa  among 
animals  in  general;  and  mal  de  cadaras,  known  in  South  America 
among  horses,  are  typical,  while  man  is  also  attacked  by  the  sleeping 


28  Ehrlich's  Chemotherapy.  { ^  January,  wu™' 

sickness  in  the  tropics.  The  scourge  of  syphilis  is  produced  by  a 
parasite  known  as  the  spirochete,  which  is  closely  allied  to  the  others 
named,  although  it  is  still  undetermined  whether  its  nature  is  animal 
or  vegetable.  As  will  be  seen,  this  particular  disease  has  been  found 
to  be  one  of  the  most  amenable  to  treatment. 

As  a  result  of  his  researches,  Ehrlich  formulated  a  theory  regard- 
ing the  behavior  of  the  cells  of  living  tissue,  or  of  parasites  toward 
foreign  bodies.  He  conceives  them  as  made  up  of  a  central  "  dom- 
inant body,"  which  throws  out  "  sidechains,"  to  which  he  later 
gave  the  name  receptors.  These  are  of  variable  character,  some 
being  nutrient  receptors,  and  others  chemo-receptors,  that  is,  recep- 
tors or  certain  definite  chemical  elements  or  groups  of  elements, 
known  in  chemistry  as  radicals.  In  a  crude  sense,  the  receptors 
may  be  likened  to  locks,  and  the  nutrient  or  chemical  bodies  as  keys, 
each  fitting  a  particular  lock,  as,  for  example,  the  dyestuff  methy- 
lene-blue  already  mentioned.  The  combinations  thus  affected  may 
be  beneficial  to  the  cell,  as  in  the  case  of  the  nutrients,  or  they  may 
result  in  the  poisoning  and  death  of  the  cell,  as  in  the  case  of  the 
methylene-blue  when  brought  into  contact  with  the  type  of  Plas- 
modium referred  to  above,  or  quinine  for  plasmodia  in  general,  a 
specific  remedy  for  malaria  discovered  by  empirical  research. 

Ehrlich  and  his  co-workers,  with  extraordinary  skill  and  industry, 
prepared  several  hundred  dye-stuffs,  studying  the  varying  effects 
of  alterations  in  chemical  structure,  each  new  compound  having  been 
logically  selected  as  the  result  of  laboratory  tests  of  its  parasiticidal 
efficiency.  Of  all  these,  very  few  finally  withstood  severe  tests,  pos- 
sibly not  more  than  ten  in  all,  but  the  fact  was  established  that  it  was 
possible  in  certain  cases  to  sterilize  the  animal  organism  with  respect 
to  parasites,  by  this  means,  without,  at  the  same  time,  poisoning  the 
animal  itself.  They  were  also  able  to  establish  certain  principles  as 
to  the  chemical  structure  of  the  dye-stuffs  most  likely  to  be  effective. 
They  encountered,  however,  many  difficulties.  A  dye  which  would 
attack  and  destroy  a  given  parasite  in  a  particular  animal  would  not 
always  do  so  in  another  species.  Symptoms  of  disease  would  some- 
times recur  after  varying  intervals,  and  the  parasites  would  then 
often  exhibit  peculiar  resistance  to  further  attack. 

While  these  researches  were  still  in  progress,  Uhlenmuth  and 
Salmon  published  an  account  of  instances  of  marked  success  in  the 
destruction  of  the  spirochete  of  syphilis,  and  the  arrest  of  the  disease, 
by  the  use  of  an  arsenical  compound  known  as  atoxyl.  Secondary 


AjanuTryPih9i4m'}  Ehrlich' s  Chemotherapy.  29 

and  seriously  harmful  effects  to  the  patients  were,  however,  the 
consequence  of  this  treatment,  but  the  parasiticidal  properties  of 
this  compound  were  so  marked  that  Ehrlich  turned  his  attention  to 
it,  in  an  attempt  to  so  modify  its  effects  upon  the  animal  organism 
which  was  harboring  the  parasites,  that  its  curative  power  might  be 
made  available. 

The  task  was  by  no  means  a  simple  one.  He  first  established  the 
composition  of  the  atoxyl  as  a  para-amido-phenyl  arsenic  acid.  The 
vast  amount  of  work  already  done  with  the  dye-stuff  indicated  certain 
lines  of  probable  success,  which,  nevertheless,  was  only  attained  on 
the  synthesis  of  the  six  hundred  and  sixth  organic  compound  by 
Ehrlich  and  Kata,  sometimes  known  as  "  606,"  and  now  designated 
salvarsan.  Chemically  it  is  dioxy-diamido-arseno-benzol,  in  which 
arsenic  is  associated  with  structural  groups  akin  to  those  found  in 
the  dye-stuffs.  A  later  preparation  "  914,"  known  as  neo-salvarsan, 
is  said  to  be  a  combination  of  a  salvarsan  with  sodium  formaldehyde 
sulphoxalate,  which  is  designed  to  overcome  a  certain  difficulty  in 
administration  of  the  salvarsan,  due  to  acidity  of  its  solutions. 

Ehrlich  assumes  that  the  parasite  of  syphilis,  the  spirochete, 
possesses  among  others,  arsenio-receptors,  and  that  through  the 
combination  with  this  arsenic  compound  the  parasite  is  poisoned  and 
dies.  Ehrlich  claims  that  in  more  than  twelve  thousand  cases  in 
which  this  drug  has  been  administered  by  him,  no  single  case  of 
poisoning  has  resulted.  The  administration  of  the  drug,  which  is 
intravenous,  or  intramuscular,  requires,  however,  considerable  skill 
and  care.  The  treatment  with  salvarsan  is  often  combined  with 
that  of  mercury.  There  seems  to  be  no  doubt  that  this  preparation 
exerts  a  specific  and  destructive  action  upon  the  spirochete,  and  has 
already  resulted  in  the  alleviation  of  an  enormous  amount  of  suf- 
fering (often  hereditary  and  undeserved)  from  this  dreadful 
scourge.  It  is  still  too  early  to  make  final  statements  as  to  the  per- 
manence of  the  cures  affected  although  there  is  much  reason  for 
hopefulness.  It  should,  however,  be  noted  that  this  chemothera- 
peutic  treatment,  unlike  the  anti-toxin  treatment  for  certain  other 
diseases,  does  not  at  all  produce  immunity  from  later  infection  from 
the  same  disease.  Indeed,  there  is  some  evidence  to  show  that  cases 
of  re-infection  are  distinctly  harder  to  treat  successfully  than  those 
of  initial  infection.  The  cure  of  advanced  cases  of  the  disease  natu- 
rally, presents  greater  difficulties,  because  of  secondary  disturbances 
of  the  vital  organs,  but  many  of  these  have  been  materially  alleviated. 


30  Ehrlich's  Chemotherapy.  { Aj J^y',  m™' 

The  progress  made  in  the  chemotherapeutic  treatment  of  diseases 
produced  by  other  trypanosomes,  notably  that  of  the  "  sleeping  sick- 
ness," has  been  less  marked  up  to  the  present.  Something  has  been 
gained,  but  no  specific  drug  comparable  with  salvarsan  in  its  effi- 
ciency has  yet  been  found. 

It  is,  however,  recorded  that  in  Surinam  a  hospital  was  estab- 
lished to  treat  cases  of  another  tropical  disease  known  as  the  yaws. 
In  the  course  of  eight  days  three  hundred  and  twenty-eight  cases 
were  admitted,  and  at  the  end  of  fourteen  days  the  last  patient  was 
discharged,  cured,  and  the  hospital  had  to  be  closed. 

In  another  field  the  work  of  Ehrlich  has  led  to  procedures  which 
are  of  the  greatest  promise  in  the  study  of  the  processes  involved 
in  the  progress  of  medical  and  physiological  research,  namely,  so- 
called  "  vital  staining."  By  means  of  the  injection  of  dye-stuffs  into 
living  organisms,  it  is  possible,  because  of  the  selective  receptivity 
of  certain  tissues  or  parasites,  for  a  particular  color,  to  trace  the 
movement  of  bacilli,  and  to  watch  the  changes  which  they  occasion 
in  the  living  organism  itself.  The  same  procedure  is  employed  in 
the  study  of  healthy  tissue. 

To  Ehrlich's  clear,  analytical  mind,  exceptional  executive  ability, 
fine  technique,  and  extraordinary  industry  is  due  not  only  the  pro- 
cedure by  which  certain  particular  diseases  may  be  arrested,  but  a 
splendid  example  of  logical  attack  upon  other  similar  problems, 
which  offers  great  promise  for  the  future,  even  though,  as  in  the  case 
of  the  anti-toxins,  one  marked  success  may  not  be  at  once  followed 
by  others  of  equal  moment.  He  has  demonstrated,  in  a  way  which 
cannot  be  detailed  in  the  scope  of  this  article,  that  the  test-tube  ex- 
periments made  in  the  laboratory  with  a  particular  drug  upon  a 
special  parasite  cannot  be  alone  relied  upon  as  an  index  of  the  effect 
upon  it  of  the  same  drug  when  it  is  harbored  by  the  living  organism, 
since  the  action  is  essentially  modified  by  that  organism,  and  he  has 
advanced  theories  which  at  least  help  in  the  understanding  of  the 
possible  reasons  for  the  variations  in  behavior  thus  observed.  Even 
though  Ehrlich's  chemotherapy  may  not  be,  in  an  exact  sense,  a  "  new 
science,"  it  must  be  acknowledged  to  be  a  most  fruitful  and  helpful 
combination  of  the  principles  of  two  well-recognized  and  time- 
honored  sciences  for  the  benefit  of  mankind. 


Am.  Jour.  Pharm.  ) 
January,  1914.  J 


Oil  of  Sandalwood. 


3i 


OIL  OF  SANDALWOOD.1 

By  E.  M.  Holmes. 

The  gradual,  but  steady,  increase  in  the  price  of  sandalwood 
oil  during  the  last  few  years  has  naturally  given  rise  to  enquiries 
concerning  its  cause.  Neither  the  growing  use  of  the  oil  for 
medicinal  purposes,  nor  the  large  demand  for  the  wood  in  India 
and  China,  can  sufficiently  account  for  it.  There  is,  however, 
a  possible  cause  that  has  apparently  not  received  the  attention  it 
deserves  from  merchants  in  this  country.  During  the  last  30  years 
or  more,  Lantana  and  Casuarina  plants  have  been  introduced  into 
sandalwood  plantations  with  the  idea  of  their  shade  helping  the 
growth  of  the  young  sandal  plants,  and  it  appears  that  concurrently 
with  a  diseased  state  of  the  Lantana,  the  sandal  plants  have  become 
affected  with  what  is  known  as  the  spike  disease. 

A  most  interesting  account  of  this  disease  is  given  by  Mr.  F.  S. 
Mason  in  the  Pharmaceutical  Journal  in  1903  (May  30th,  p.  756), 
which  gives  an  excellent  idea  of  the  character  of  the  disease,  and 
of  the  extent  to  which  the  plantations  are  affected.  One  remark 
in  this  paper  is  well  worthy  of  notice,  viz.,  that  "  within  five  years 
it  has  swept  whole  tracts  of  country,  and  unless  some  means  can  be 
devised  to  check  its  ravages,  it  is  only  a  question  of  time  for  the 
plant  to  become  very  rare,  if  not  extinct."  So  convinced  was  the 
Mysore  Government  of  the  importance  of  rinding  a  means  to  check 
the  disease,  that  in  1907  the  Maharajah  of  Mysore  offered  a  prize 
of  10,000  rupees  to  anyone  who  could  discover  the  cause  of  the 
disease,  and  devise  a  curative  treatment  for  it.  But  although  the 
offer  remained  open  until  19 10  no  one  succeeded  in  winning  the 
prize. 

The  cause  of  the  disease  was  investigated  on  behalf  of  the 
Indian  Government  by  Mr.  Barber  and  Dr.  Butler,  and  they  came 
to  the  conclusion  that  it  was  not  due  to  any  animal  or  vegetable 
parasite,  but  was  connected  with  the  disc-like  suckers  at  the  ex- 
tremities of  the  roots  of  the  sandalwood  tree,  by  which  it  attaches 
itself  to  the  roots  of  other  plants  and  obtains  nourishment  from 
them  (Indian  Forester,  xxxiii,  1907,  p.  199).  That  no  curative 
means  of  arresting  the  disease  has  yet  been  devised  is  evident  from 


^he  Perfumery  and  Essential  Oil  Record,  June,  1913,  161. 


Oil  of  Sandalwood. 


Am.  Jour.  Pharm. 
January,  1914. 


a  statement  published  last  October  in  the  same  journal,  to  the 
effect  that  the  disease  still  continues  with  dire  results,  and  that 
in  two  districts  alone  some  70,000  sandal  trees  had  to  be  uprooted. 

In  order  to  obtain  an  idea  of  the  probable  cause  of  this  disease 
it  is  necessary  to  pay  some  attention  to  the  life  history  of  the  plant, 
so  far  as  this  is  known.  As  already  mentioned,  the  sandal  tree 
is  a  root  parasite,  obtaining  its  food  by  means  of  suckers,  which  it 
attaches  to  the  roots  of  other  trees.  It  has  been  ascertained  by 
Rama  Rao  that  there  are  at  least  144  species  of  plants  which  the 
sandal  tree  attacks  in  this  way,  as  proved  by  experiment  with  sandal- 
wood seedlings,  and  he  gives  a  list  of  252  plants  which  are  found 
growing  near  or  with  the  sandal  tree,  but  are  as  yet  not  known  to  be 
utilized  as  a  source  of  food  by  this  tree.  It  does  not  appear  to  be 
equally  nourished  by  all  of  its  host  plants,  and  the  condition  of  the 
tree  depends  upon  the  vigorous  and  healthy  state  of  its  host.  Thus 
it  is  known  that  a  plant  on  which  it  will  thrive  in  one  district  fails 
to  keep  it  in  a  healthy  state  in  another,  where  the  conditions  are 
unsuitable  to  the  healthy  growth  of  the  host  plant.  This  require- 
ment of  the  sandalwood  tree  is  well  shown  by  an  observation 
recorded  in  the  Indian  Forester,  (xxxl,  p.  191),  that  when  a  trunk 
of  Heptapleurum  was  cut  down,  the  sandal  plant  attached  to  its 
roots  began  to  wither,  but  when  new  shoots  formed  on  it  the  sandal 
plant  began  to  revive.  The  sandalwood  tree  sends  out  roots  for 
150  feet  or  more,  and  therefore  requires  a  comparatively  loose 
and  well-drained  soil  which  the  roots  can  easily  penetrate  and 
spread  in.  In  a  natural  state  it  flourishes  at  an  altitude  of  1500 
to  4000  ft.,  the  best  yield  of  oil  being  obtained  from  trees  growing 
between  2000  to  3500  ft.,  on  loose  volcanic  soil  mixed  with  rocks, 
and  preferably  ferruginous  in  character.  It  requires  to  be  shaded 
by  thickets  above  which  it  can  form  a  head  of  leafy  branches. 

Although  in  rich  soil  it  grows  more  luxuriantly,  less  scented 
wood  is  formed,  although,  as  the  tree  furnishes  more  wood,  the 
proportion  is  about  the  same.  It  is  considered  that  the  richness  of 
the  wood  in  oil  depends  more  upon  elevation  and  exposure,  since, 
although  the  tree  grows  luxuriantly  at  700  ft.,  the  wood  is  said  to  be 
totally  devoid  of  scent  at  that  altitude  (Indian  Forester,  xxvl, 
pp.  1-50,  1900). 

The  experiments  made  by  Rama  Rao  indicate  that  the  physical 
conditions  of  soil  and  drainage  affect  the  development  of  the  root- 
branching  system.    The  soil  needs  to  be  well  drained,  as  the  seed 


Am.  Jour.  Pharm.  \ 
January,  1914.  j 


Oil  of  Sandalwood. 


33 


rots  in  soil  where  stagnant  water  is  present,  more  readily  than  in 
most  plants. 

The  seed  of  the  sandalwood  tree  germinates  freely  in  the  thickets 
where  the  tree  grows,  within  a  month  of  being  sown,  although 
germination  may  occur  any  time  during  three  months  or  longer, 
but  if  the  seed  germinates  in  open  ground  where  it  does  not  meet 
with  other  roots,  the  seedlings  soon  wither  and  die.  The  young 
plants  for  plantations  must  therefore  be  raised  by  planting  them 
with  other  plants  on  whose  roots  the  seedlings  can  feed  as  soon 
as  they  have  exhausted  the  nourishment  of  their  own  seed  lobes, 
which  lasts  for  about  two  months.  The  seeds  are  therefore  planted 
in  short  wide  tile  tubes  resembling  drain  pipes,  but  shorter,  so  that 
the  young  seedlings  can  be  planted  out  without  disturbing  their 
root  attachments.  This  planting  out  is  done  when  they  are  about 
4  ins.  high  or  rather  more  than  a  year  old.  If  allowed  to  grow 
larger  there  is  likely  to  be  injury  done  to  the  roots  in  planting  them 
out.  After  planting  out,  the  seedlings  require  to  be  gently  but 
copiously  watered  until  well  established. 

Experiment  has  shown  that  the  best  plants  to  grow  with  the 
seedlings  are  Pongamia  glabra,  Gossypium  arboreum,  Albizzia,  Leb- 
bek  and  Cleistanthus  collinus. 

The  seedlings  need  protection  from  animals,  as  the  foliage  of  the 
sandalwood  plants  proves  very  attractive  to  them.  Cattle  and  goats 
will  greedily  eat  the  foliage  whenever  they  see  it,  and  deer  will 
leap  over  the  obstructing  bushes  to  get  at  it,  and  hares  will  creep 
through  the  thicket  to  reach  it. 

As  the  seedlings  in  a  wild  state  reach  only  a  height  of  3  ins. 
the  first  year,  and  12  ins.  the  second  year,  they  are  easily  destroyed. 
It  is  only  in  the  fifth  or  sixth  year  they  appear  above  the  surround- 
ing bushes  and  form  a  leafy  head.  At  this  time  the  stem  is  about 
1  in.  in  diameter. 

It  takes  18  to  25  years  before  the  tree  is  fit  to  yield  oil.  With 
respect  to  the  spike  disease,  the  trees  attacked  by  it  present  the 
appearance  of  being  dead,  but  on  careful  examination  many  leaves 
are  seen  to  be  scattered  over  the  tree  at  the  end  of  the  stiff  branches, 
but  they  are  very  small,  and  form  small  terminal  tufts,  hence  the 
name  "  Spike  "  disease.  The  shoots  are  found  to  be  full  of  starch, 
indicating  that  the  plant  has  not  been  able  to  utilize  its  stored-up 
nourishment.    The  disease  is  pronounced  to  be  infectious,  because 


34 


Oil  of  Sandalwood. 


(Am.  Jour.  Pharm. 
\    January,  1914. 


all  sandal  plants,  in  plantations  where  it  occurs,  have  died,  whilst 
solitary  trees  are  still  thriving. 

From  the  above  facts,  recorded  by  various  observers,  it  becomes 
evident  that  the  sandalwood  tree  requires  plenty  of  room  so  as  to 
be  able  to  select  vigorous  hosts  to  feed  it;  that  it  requires  soil  por- 
ous enough  to  enable  its  roots  to  spread  readily,  and  that,  therefore, 
if  too  closely  planted,  it  may  easily  be  starved,  especially  in  hard  or 
heavy  soil.  The  fact  that  isolated  trees  thrive  in  a  natural  condition 
also  indicates  that  the  disease  is  one  of  mal-nutrition,  whilst  the 
presence  of  starch  in  the  withered  shoots  indicates  the  absence  of 
a  suitable  enzyme  to  transform  it  into  soluble  food. 

Apparently  no  attempts  have  as  yet  been  made  to  ascertain  the 
chemical  constituents  that  the  tree  contains,  and  therefore  needs, 
although  Peterson  (Pharmaceutical  Journal  (3),  xvl,  page  575) 
found  that  Macassar  sandalwood  was  rich  in  iron  (7.5  pc)  and 
contained  traces  of  manganese.  The  latter  metal  is  believed  to  be 
connected  with  the  activity  of  enzymes,  and  it  is  possible  that  a 
deficiency  of  it  in  the  soil  may  injuriously  affect  the  growth.  Re- 
search is  also  evidently  necessary  to  ascertain  if  the  tree  selects  one 
ingredient  for  its  nourishment  from  one  tree  and  other  ingredients 
from  other  species,  as  it  is  well  known  that  certain  enzymes  can 
split  up  other  bodies  than  those  on  which  they  usually  act. 

There  is  evidently  much  to  be  done  before  the  cause  of  the 
disease  and  the  means  to  prevent  it  can  be  ascertained. 

Regarding  the  subject  from  the  commercial  side,  the  possibility 
of  other  sources  of  sandalwood  suggests  itself.  The  world's  supply 
of  sandalwood  oil  is  at  the  present  time  chiefly  derived  from  the 
trees  grown  in  Southern  India,  only  a  comparatively  small  quantity 
coming  from  the  Islands  of  Timor  and  Sumba  via  Macassar.  The 
yield  from  Mysore  last  year  was  2469  tons  of  sandalwood,  exclusive 
of  chips  and  sawdust.  The  average  price,  including  chips  and  saw- 
dust, was  471  rupees  as  against  461  rupees  per  ton  during  the 
previous  decennial  period. 

The  only  other  oil  that  at  present  competes  with  the  East  Indian 
sandalwood  oil  is  that  of  Amyris  balsamifera  L.,  a  tree  belonging 
to  the  natural  order  Burseracese,  the  wood  of  which  is  imported 
from  Venezuela,  and  is  known  in  Europe  as  West  Indian  sandal- 
wood. It  competes,  however,  only  in  medicinal  use,  not  in  per- 
fumery. 

Of  the  20  or  more  known  species  of  Santalum,  which  are  dis- 


Am.  Jour.  Pharm.  \ 
January,  1914.  j 


Oil  of  Sandalwood. 


35 


tributed  over  Asia,  Australia,  New  Caledonia  and  Polynesia,  several 
were  rendered  almost  extinct  by  the  ruthless  destruction  of  the 
trees  during  the  first  half  of  the  last  century,  and  are  not  now 
available  in  quantity  for  commercial  purposes.  These  include 
5\  Freycinetianum,  Gaud.,  of  the  Sandwich  Islands,  S.  Hornet, 
Seem.,  of  Eromanga,  S.  insular e,  Bert.,  of  the  Marquesas  and  Do- 
ciety  Islands,  and  5\  Yasi,  Seem.,  of  the  Tongo  Islands,  and  5.  Aus- 
tro-Caledonicum,  VieilL,  of  New  Caledonia.  The  wood  of  these 
trees  was  chiefly  collected  for  the  Chinese  market,  and  not  for  the 
distillation  of  oil.  None  of  these  trees,  so  far  as  is  known,  yields 
an  oil  equal  in  fragrance  to  that  of  5".  album. 

A  log  of  wood  of  Santalum  Yasi  from  the  Indian  and  Colonial 
Exhibition  was  distilled  by  Mr.  C.  Umney  in  1886,  and  a  sample  of 
the  oil  sent  to  Messrs.  Schimmel  and  Co.,  who  considered  it  in- 
ferior both  in  perfume  and  therapeutical  effect  to  that  of  Santalum 
album.  The  yield  appeared  to  be  6y2  per  cent.,  although  the  real 
percentage  might  have  been  less,  as  an  unusual  amount  of  water 
separated  from  the  oil  in  the  winter  weather. 

Of  the  trees  yielding  sandalwood  in  Australia,  some  of  which 
were  formerly  classed  in  the  genus  Santalum,  the  oils  are  known 
only  in  a  few  cases.  That  of  Fusanus  spicatus  R.  Br.  (formerly 
Santalum  cygnorum)  or  West  Australian  sandalwood  oil,  is  dis- 
tilled to  some  extent  in  West  Australia,  but  is  considered  by 
Gildemeister  and  Hoffmann  to  have  an  unpleasant  resinous  odor, 
and  not  fit  to  be  used  as  a  substitute  for  East  Indian  sandalwood  oil. 
It  is,  however,  the  nearest  to  the  true  sandalwood  oil,  and  contains 
75  per  cent,  of  alcohols,  which  have,  however,  not  been  positively 
identified  with  santalol,  but  owing  to  the  small  yield  of  oil  (2  per 
cent.)  and  the  expense  of  labor  in  Australia,  although  the  tree 
is  fairly  plentiful,  it  cannot  compete  with  the  Indian  oil.  That  of 
F.  acuminatus  R.  Br.  (formerly  Santalum  Preissianum  Miq.) 
known  as  South  Australian  sandalwood,  yields  a  vivid  cherry-red 
oil,  from  which  crystals  separate  out  on  cooling.  It  has  a  different, 
somewhat  rose-like  odor,  and  a  different  composition  and  specific 
gravity  to  that  of  East  Indian  sandalwood.  Exocarpus  latifolius 
R.  Br.,  a  West  Australian  plant,  may  perhaps  yield  some  of  the 
West  Australian  sandalwood  oil,  but  there  is  no  evidence  that  it 
yields  an  oil  resembling  that  of  true  sandalwood. 

Several  fragrant  woods  are  known  under  the  name  of  sandal- 
wood in  other  countries;  the  wood  of  Osyris  tenuifolia,  Engl.,  a 


36 


Oil  of  Sandalwood. 


{Am.  Jour.  Pharm. 
January,  1914. 


native  of  Kilmandscharo,  in  East  Africa,  has  been  imported  into 
Germany  under  the  name  of  East  African  sandalwood.  The  oil 
was  described  in  1908  as  being  bright  brown  in  color  with  an  odor 
intermediate  between  that  of  vetivert  and  gurjun  balsam,  but  quite 
different  from  sandalwood  (Pflanzenweldt  Ost.  Afrika  C.  167, 
Schimmel's  Report,  November,  1908,  p.  109). 

The  Madagascar  "  Sandalwood,"  of  which  the  native  name  is 
apparently  "  Hasoranto,"  is  exported  from  Tamatave  in  the  North 
of  Madagascar  to  Zanzibar,  and  thence  to  Bombay,  where  it  is 
known  as  taggar  wood,  and  is  largely  used  as  a  cheap  substitute  for 
sandalwood  for  funeral  pyres.  The  wood  is  of  a  dark  brown 
color,  and  yields  a  dark-colored  thick  oil,  with  an  odor  slightly 
resembling  sandalwood,  but  which  for  medicinal  or  perfumery 
purposes  could  by  no  means  be  used  as  a  substitute  for  it.  Its 
botanical  source  is  unknown,  but  is  supposed  to  be  a  Lauraceous 
tree. 

New  Zealand  Sandalwood. — The  wood  of  Olearia  Traversii, 
F.  Muell,  was  exhibited  at  the  International  Exhibition  in  1886 
under  the  name  of  bastard  sandalwood.  It  belongs  to  the  Family 
of  Compositae,  but  nothing  appears  to  be  known  of  its  oil. 

Cochin  China  Sandalwood. — This  is  ascribed  by  Baillon  to 
Epicharis  Loureirii,  Pierre,  Fam.  Melacese,  but  I  have  not  seen  a 
specimen. 

Guiana  Sandalwood. — The  oil  has  already  been  described 
(P.  &  E.  O.  R.,  191 1,  p.  79).  Dr.  Giessler,  of  Leipzig,  is  of  opinion 
that  the  oil  is  probably  derived  from  three  species  of  the  genus 
Acrodiclidium,  or  Ocotea  (Schimmel's  Report,  October,  191 1, 
p.  82).  It  does  not  resemble  sandalwood  oil  in  odor  and  is  not 
known  to  do  so  therapeutically. 

Ibean  Sandalwood. — The  wood  of  Brachylana  Hutchinsii, 
Hutchinson  (Family  Composite),  is  known  under  this  name. 
The  tree  grows  near  Nhairobi  and  in  forests  near  the  coast  at  an 
elevation  of  5000  to  6000  feet.  The  timber  is  white,  hard,  easily 
worked,  and  scented  when  freshly  cut,  and  is  not  subject  to  the 
attacks  of  white  ants.  The  native  name  of  the  tree  is  "  Muhugu." 
It  does  not  appear  to  have  been  exported  as  yet,  the  tree  being  only 
described  three  years  ago  in  the  Kew  Bulletin,  1910,  p.  126.  The 
plant  is  illustrated  in  the  Icones  Plantarum,  292a. 

It  is  obvious,  therefore,  that  at  present  there  is  no  oil  known 
that  can  altogether  take  the  place  of  sandalwood  oil,  and  until  a 


AjanJuTry,Pi9i4m*}  Pa-  State  Pharmaceutical  Association.  37 

means  of  combating  the  spike  disease  has  been  discovered  and  the 
best  method  of  cultivation  of  the  tree  has  been  ascertained,  the 
price  of  sandalwood  is  likely  to  rise,  especially  since  it  takes  from 
18  to  25  years  for  the  tree  to  arrive  at  maturity  and  to  grow 
scented  wood. 

The  chemical  constitution  of  the  oil  does  not  hold  out  much 
hope  that  it  will  be  an  easy  matter  to  produce  it  synthetically,  for 
even  if  santalol  can  be  produced  from  piperidine,  there  are  evidently 
other  constituents  that  go  to  form  the  odor  of  the  oil,  and  unless 
these  can  be  ascertained  it  is  not  likely  to  take  the  same  place 
in  perfumery  or  medicine  as  the  oil  distilled  from  Santalum  album. 


ABSTRACTS  OF  SOME  PAPERS  READ  AT  THE  1913 
MEETING  OF  THE  PENNSYLVANIA  STATE 
PHARMACEUTICAL  ASSOCIATION. 

By  John  K.  Thum,  Ph.G.,  Philadelphia,  Pa. 

What  is  the  Quality  of  Pancreatin  on  the  Market? 

By  Charles  H.  La  Wall. 

An  examination  of  some  pancreiatin  by  the  author  disclosed  the 
interesting  fact  that  it  was  adulterated  with  powdered  malt.  Of 
course  this  raised  the  starch  converting  power,  and,  as  the  author 
states,  as  this  test  is  the  only  one  applied  sometimes  and  as  the 
general  appearance  of  such  a  sophisticated  sample  is  normal,  a  more 
than  superficial  examination  of  pancreiatin  is  necessary  to  insure 
good  quality. 

Sterilization  in  Pharmacy. 

By  A.  Parker  Hitchens,  M.D. 

The  author  in  a  very  interesting  and  illuminative  manner  de- 
scribes the  possible  purposes  of  sterlization  in  pharmacy  and  gives 
in  detail  the  various  methods  which  have  been  found  to*  be  of  value. 

Crotalin — Collection,  Preservation,  Chemistry  and  Action. 
By  Walter  Roth  well. 

Attenuated  snake  venom,  obtained  from  Crotalus  Horridus, 
commonly  known  as  "  rattlesnake,"  has  obtained  some  vogue  in 
recent  years  in  the  treatment  of  epilepsy.    The  author  briefly  de- 


38  Pa,  State  Pharmaceutical  Association.  {AjanJu°a^;  ^In- 

scribes the  method  of  obtaining  the  venom,  its  preservation,  chemis- 
try, and  action.  It  is  given  hypodermatically  and  its  action  is  to 
increase  the  time  of  the  coagulation  of  the  blood. 

The  Detection  of  Cane  Sugar  in  Honey. 

By  Charles  LaWall,  Ph.M. 

The  author  concludes  that  it  is  impossible  to  detect  added  cane 
sugar  in  honey  by  means  of  a  qualitative  test ;  being  present  normally 
in  small  amounts  its  quanitative  determination  is  preferably  accom- 
plished by  means  of  the  polariscope.  Invert  sugar  is  the  kind 
usually  added  and  dan  be  easily  detected  in  honey  that  has  never 
been  heated. 

Oregon  and  Canada  Balsam  of  Fir. 

By  J.  G.  Roberts  and  M.  M.  Becker. 

The  writers  state  that  because  of  the  scarcity  of  Canada  Balsam 
of  Fir  for  the  last  year  or  two  a  suitable  substitute  is  desirable. 
And  as  a  substitute  Oregon  Balsam  of  Fir  is  offered  to  the  trade. 
As  is  well  known  this  product  closely  resembles  Canada  Balsam  of 
Fir. 

Finding  that  the  literature  on  Oregon  Balsam  contained  little 
information  the  authors  obtained  some  balsam  from  a  known  source 
and  endeavored  to  obtain  data  as  to  tests  for  identity  and  purity. 

It  differed  in  the  main  from  Canada  Balsam  in  viscosity,  solu- 
bility in  alcohol,  and  in  response  to  the  magnesium  oxide  test.  The 
Oregon  Balsam  is  thinner;  it  is  completely  soluble  in  alcohol  in 
contradistinction  to  the  official  balsam  which  yields  a  turbid  solu- 
tion. Canada  Balsam  when  mixed  with  20  per  cent,  of  its  weight 
of  magnesium  oxide  previously  moistened  with  water,  becomes 
solid.  The  Oregon  does  not  solidify  even  when  mixed  with  60  per 
cent,  of  its  weight  of  magnesium  oxide.  It  was  also  noticed  that 
the  Oregon  Balsam  does  not  dry  as  readily  as  the  Canada  Balsam, 
a  quality  which  renders  it  inferior  to  the  latter  for  microscopical 
work. 

Socotrine  Aloes. 

By  C.  J.  Denneby. 

The  author  remarks  that  although  the  United  States  Pharma- 
copoeia definition  of  aloes  is  broad  enough  to  allow  recognition  of 
all  varieties  of  genuine  aloes  yet  it  neglects  to  describe  some  samples 


Am.  Jour.  Pharm.  \ 
January,  1914.  / 


Book  Reviews. 


39 


as  imported.  It  is  often  received  in  barrels  in  a  pasty  condition, 
containing  nearly  twice  the  amount  of  water  permitted  by  the 
U.  S.  P.  It  is  further  remarked  by  the  author  that  when  in  this 
condition  the  only  recourse  is  rejection  of  the  shipment  as  abnormal 
as  to  its  physical  appearance,  or,  it  being  satisfactory  as  to  identity 
and  purity,  to  dry  so  that  sample  is  of  proper  U.  S.  P.  quality.  A 
tabulation  of  five  samples  is  given ;  all  contained  twice  the  quantity 
of  water  allowable ;  they  also  failed  to  pass  the  alcohol  test  for 
limit  of  gums,  dextrins  and  impurities.  While  Kraemer  and  others 
state  that  aloes  should  not  yield  more  than  4  per  cent,  of  ash  all  of 
these  samples  were  slightly  higher.  As  is  well  known  and  has  been 
for  some  time,  no  aloes  is  obtained  from  Soeotra. 

The  Microscopic  Examination  of  Ointments. 

By  Fritz  Heidlberg  and  Chas.  E.  Vanderkleed. 

The  value  of  an  ointment,  the  authors  state,  consists  mainly  in 
the  fineness  or  subdivision  of  the  active  ingredient  suspended  in 
the  vehicle.  And  to  properly  determine  when  the  ointment  has 
been  manipulated  long  enough  for  the  active  ingredient  to  be  uni- 
formly and  evenly  divided  they  advise  the  use  of  the  microscope. 
They  state  that  this  is  the  only  satisfactory  way  to  tell  whether 
uniform  results  have  been  obtained.  They  also  give  their  technic 
for  preparing  slides  for  this  purpose  and  illustrate  by  showing 
micro-pho'togriaphs  of  mercury  ointments. 


BOOK  REVIEWS. 

Digest  of  Comments  on  the  Pharmacopoeia  of  the  United 
States  of  America  (8th  Decennial  Revision)  and  on  the 
National  Formulary  (3RD  Edition)  for  the  Calendar  Year 
Ending  December  31,  191  i.  By  Murray  Gait  Motter  and  Martin 
I.  Wilbert. 

The  foregoing  title,  known  also  as  Bulletin  No.  87,  Hygienic 
Laboratory,  needs  little  introduction  to  the  progressive  members 
of  the  pharmaceutical  profession.  It  speaks  for  itself.  It  is  suffi- 
cient to  say  that  the  literature  covered  in  this  review  embraces 
matters  that  must,  if  thoroughly  and  painstakingly  studied  by  the 


40 


Book  Reviews. 


(  Am.  Jour.  Pharm. 
\    January,  1914. 


two  revision  committees,  result  in  the  publication  of  a  Pharmaco- 
poeia and  National  Formulary  that  will  be  regarded  as  authoritative 
and  the  last  word  in  pharmaceutical  matters. 

References  to  the  great  mass  of  literature  consulted  is  com- 
plete in  every  respect  and  comments  relating  to  the  legal  status  and 
development  of  pure  food  and  drug  laws,  scope,  analytical  data, 
clinical  tests,  biologic  products  and  vegetable  drugs  are  abstracted 
with  the  main  points  of  the  papers  brought  out.  This  is  as  it  should 
be,  as  it  enables  a  worker  to  see  at  once  if  a  reference  is  worth  while 
consulting. 

It  is  particularly  gratifying  to  note  that  references  of  a  practical 
nature  in  regard  to  pharmaceutical  preparations  and  suggestions  as 
to  their  improvement,  both  as  to  formula  and  method  of  prepara- 
tion, are  much  in  evidence. 

The  "  digest  "  also  places  at  the  disposal  of  the  revision  com- 
mittees references  to  all  literature  pertaining  to  international 
standards.  Every  decade  brings  us  closer  to  a  realization  of  the 
fact  that  the  question  of  unification  of  pharmacopceial  preparations 
is  becoming  a  matter  of  supreme  importance.  Rapid  means  of  travel 
and  communication  are  largely  responsible  for  this. 

Foreign  Pharmacopoeias  always  bring  forth  considerable  comment 
and  criticism  from  workers  and  experts  from  various  parts  of  the 
globe  and  last  year  was  no  exception.  The  collaborators  of  the 
"  Digest  "  make  this  fact  plain  in  their  references  to  literature  that 
comments  on  the  German,  Russian,  Italian,  French,  Swedish,  Swiss, 
Austrian,  Japanese,  Dutch,  and  British  Pharmacopoeias  and  the 
British  Pharmaceutical  Codex. 

Part  III  of  this  Bulletin  is  devoted  to  a  most  comprehensive 
review  of  the  literature  relating  to>  comments  on  official  articles 
504  pages  being  required  to  show  what  has  been  said  and  done  in 
this  field  of  endeavor,  and  also  illustrating  what  a  tremendous 
amount  of  reading  the  preparation  of  this  valuable  government 
publication  required  for  its  completion. 

John  K.  Thum. 

The  Propaganda  for  Reform  in  Proprietary  Medicines. 
Reprinted  from  the  Journal  of  the  American  Medical  Association. 
Eighth  Edition,  1913. 

There  are  many  people  who  take  as  gospel  truth  anything  they 
see  in  print.    There  are  a  great  many  other  people  who,  while  they 


Am.  Jour.  Pharm.  ) 
January,  1914.  J 


Book  Reviews. 


41 


know  better  than  to  do  this,  are  unable  to  discriminate  and  so  are 
almost  as  easily  led  as  the  others.  Then  there  are  many  people 
afflicted  with  some  ailment,  or  think  that  they  are,  who  clutch,  like 
a  drowning  man  after  a  straw,  any  statement  which  seems  to  bear 
upon  their  case. 

To  satisfy  the  "  needs  "  of  people  like  these  there  is  a  host  of 
firms  who  manufacture  remedies  for  every  conceivable  trouble,  and  to 
eliminate  the  need  of  having  a  physician  they  include  in  their  packages 
circulars  which  purport  to  give  complete  directions  of  use.  So 
extraordinary  are  some  of  these  statements  that  anyone  even  only 
very  superficially  acquainted  with  the  facts  would  prick  up  his  ears 
at  hearing  them.  But  not  so  with  the  gullible  public.  The  more 
extreme  the  statement,  the  more  absolute  dependence  they  place  on 
the  product. 

Truly,  this  proprietary  medicine  venture  is  no  more  than  a 
psychological  game  between  the  manufacturer  and  the  public,  only 
the  public  is  not  aware  that  it  is  playing  the  game.  Here  are  some 
of  the  psychological  weapons  the  manufacturer  has  at  his  command  : 

1.  As  one  bows  down  to  a  man  who  is  well  dressed  and  imposing 
in  appearance,  so  one  worships  an  ordinary  drug  or  food  (or  even  a 
worthless  one)  when  it  is  clothed  in  a  dignified  name. 

2.  As  the  average  illogical  mind  believes  that  what  comes  after 
must  be  due  to  what  goes  before,  the  deduction  is  easily  made  that 
if  a  person  recovers  after  having  made  use  of  some  remedy,  the 
remedy  deserves  the  credit.  This  is  termed  the  post  hoc,  ergo  propter 
hoc  argument.  The  folly  of  course  lies  in  the  fact  that  in  the  great 
percentage  of  cases  the  patient  would  have  recovered  without  any 
remedy. 

Yes,  the  Propaganda  for  Reform  in  Proprietary  Medicines,  which 
is  a  bound  volume  of  reprints,  might  well  be  called  "  A  Study  in 
the  Psychology  of  Advertising  Worthless  Products."  A  former 
book  of  reprints  entitled  "  Nostrums  and  Quackery "  is  relative 
especially  to  those  nostrums  which  are  exploited  only — or  chiefly — 
to  the  public.  The  volume  under  consideration,  however,  relates  to 
those  products  which  are  exploited  to  the  physician  and  includes 
also  some  of  those  in  the  other -volume  where  there  seemed  to  be  an 
"  overlapping." 

Some  120  proprietaries  are  considered,  the  schemes  by  which 
they  are  foisted  upon  the  public  through  the  medical  profession  are 
discussed  with  numerous  reproductions  of  illustrations  of  advertise- 


42 


Book  Reviews. 


{Am.  Jour.  Pharm. 
January,  1914. 


ments,  and  chemical  formulas  and  therapeutic  properties  are  given. 

A  striking  feature  is  the  prominence  which  must  be  taken  by 
the  products  of  large  well-known  manufacturing  houses  who  are 
making  a  mighty  good  thing  out  of  the  credulity  of  the  public  with 
no  regard  to  the  ethics  of  the  profession. 

A.  K.  Lobeck. 

ARBEITEN  AUS  DEM  Ph ARM AZEUTISCHEN  INSTITUT  DER  UnIVER- 

sitat  Berlin,  by  H.  Thorns,  v.  10,  including  the  work  of  the  year 
191 2,  Urban  &  Schwarzenberg,  Berlin,  Wien,  191 3,  220  pages,  with 
two  illustrations. 

This  volume  like  the  ones  preceding  it  reflects  the  work  done  in 
the  Pharmaceutical  Institute  of  the  University  of  Berlin,  by  Prof. 
Thorns  and  his  associates,  and  includes  a  total  of  35  contributions, 
under  five  general  headings:  1,  Contributions  from  the  division  for 
the  examination  of  drugs,  specialties  and  secret  remedies ;  2,  reports 
on  organic  chemical  work ;  3,  microchemical  work ;  4,  reports  from 
the  division  for  the  examination  of  foods  and  technical  products  of 
the  Colonies ;  5,  general  discussion.  The  whole  is  followed  by  an 
index  of  four  double  column  pages.  The  first  section  of  the  book 
includes  a  systematic  review  of  the  new  remedies  introduced  during 
the  year  191 2,  and  reports  the  analytical  examination  of  a  number 
of  proprietary  preparations.  The  phytochemical  work  reported  in 
this  volume  includes  observations  on  the  production  of  menthol  in 
Germany  and  in  the  German  Colonies,  and  an  examination  of  the 
seed  of  Strychnos  kongofera  for  strychnine.  Lenz  discusses  the  pro- 
duction and  use  of  microchemical  reagents  in  a  paper  covering  eight 
pages,  and  Thorns,  in  a  very  comprehensive  paper,  reviews  the 
problems  of  pharmaceutical  education  in  Germany  and  other 
European  countries. 

Altogether  the  volume  is  well  up  to  the  high  standard  that  has 
been  established  by  those  preceding  it  and  the  renewed  energy  with 
which  the  work  on  so-called  new  remedies  is  being  prosecuted  bodes 
well  for  the  general  progress  of  pharmacy  along  satisfactory  lines. 

M.  I.  W. 

ARBEITEN  AUS  DEM  Ph  ARM  AZEUTISCHEN  INSTITUT  DER  UNIVER- 

sitat  Berlin,  herausgegeben  von,  Prof.  Dr.  H.  Thorns. 

This  publication,  the  tenth  annual  volume,  consisting  of  220 
pages,  presents  a  record  of  the  work  accomplished  during  1912  at 


Am.  Jour.  Pharm.  1 
January,  1914.  j 


Book  Reviews 


43 


the  Pharmaceutical  Institute  of  the  University  of  Berlin  under  the 
direction  of  Dr.  H.  Thorns,  the  Director. 

It  also  gives  evidence  that  the  German  pharmacist,  acting 
through  this  pharmaceutical  institute,  is  alive  to  the  need  of  pro- 
tecting the  medical  profession  and  the  public  against  fraud,  secret 
medicines  and  mendacious  advertising.  Here,  in  our  own  country, 
the  pharmacists  have  been  so  busy  worrying  about  price  protection 
on  nostrums  and  telephone  rates  that  the  medical  profession  took  the 
bull  by  the  horns,  so  to  speak,  and  through  its  national  organization, 
the  American  Medical  Association,  organized  a  permanent  com- 
mittee, and  named  it  the  Council  on  Pharmacy  and  Chemistry. 
What  this  council  has  done  since  its  organization  is  known  to  a1l 
progressive  pharmacists.  And  its  efforts  for  better  things  are  surely 
showing  results.  One  has  but  to  glance  over  the  proceedings  and 
reports  of  some  of  the  medical  and  pharmaceutical  societies  to  realize 
that  we  are  at  the  dawn  of  a  new  era  as  to  things  pertaining  to 
these  two  professions. 

The  investigations  of  the  laboratory  workers  of  this  German 
institution  covered  a  wide  field  in  the  domain  of  synthetic  chemistry, 
particularly  as  regards  the  output  of  the  dye  houses  of  that  country, 
specialties  of  all  kinds,  and  secret  remedies  and  nostrums  of  all 
kinds. 

Under  the  classification  of  Analgesics,  Antipyretics,  and  Anti- 
rheumatics, considerable  attention  is  given  to  such  chemicals  as 
Melubrin,  one  of  the  more  recent  antipyretics,  said  to  be  useful  in 
rheumatism  and  resembling  in  its  effects  the  salicylates,  chemically 
it  is  sodium-phenyl-dimethyl-pyrazolon-amido-methan-sulphonate ; 
Atophan,  said  to  be  useful  as  an  antirheumatic  in  so  far  as  it  aids  in 
the  elimination  of  uric  acid  and  chemically  known  as  phenyl-quinolin- 
carboxylic  acid ;  Novatophan  a  modification  of  atophan  and  taste- 
less while  the  latter  is  bitter  ;  Aspirin  Soluble  which  is  the  calcium 
salt  of  acetyl-salicylic  acid ;  Luminal,  a  sedative  and  hypnotic,  the 
chemical  name  of  which  is  phenylethylmalonylurea ;  Brophenin,  a 
combination  of  bromine  with  phenetidin  and  chemically  known  as 
bromisovalerylamino-acetate-p-phenetidin  ;  many  others  too  numer- 
ous to  mention  are  also  considered. 

Besides  giving  considerable  space  in  this  publication  to  the  in- 
vestigation of  products  (Kolonialprodukte)  from  the  German 
colonies,  both  as  to  their  chemistry  and  pharmacognosy,  there  also 
appears  an  exposure  of  some  of  the  nostrum  emmenagogues  found 


44 


Book  Reviezvs. 


i  Am.  Jour.  Pharm. 
I    January,  1914. 


on  the  German  market.  One  of  these  consisted  of  small  quantities 
of  oil  of  cinnamon  and  cloves  in  12  per  cent,  of  alcohol.  For  two 
ounces  of  this  wonderful  and  efficient  (?)  preparation  the  modest 
sum  of  one  dollar  was  asked.  Another,  called  "  Menstruationpulver  " 
consisted  of  a  very  poor  quality  of  powdered  Roman  Chamomile, 
and  for  the  small  (?)  sum  of  seventy-five  cents  the  buyer  received  a 
package  containing  35  grammes. 

An  interesting  report  is  given  of  an  examination  of  a  fixed  oil 
sent  to  the  Institute  by  a  German  missionary  pastor  from  Venezuela. 
This  oil  is  used  by  the  Indians  in  the  region  of  Orinoco  as  a  remedy 
in  the  treatment  of  tuberculosis.  The  results  are  reported  as  good. 
This  oil  is  yellow  in  color,  slightly  cloudy,  and  in  odor  and  taste 
somewhat  resembling  olive  oil ;  at  room  temperature  fluid ;  on  cool- 
ing there  was  separated  a  small  mass  of  fatty  acid  which,  on  warm- 
ing, disappeared.  At  120  C.  the  oil  congealed  to  a  soft  butter-like 
mass.  It  was  miscible  in  all  proportions  with  ether,  chloroform, 
petroleum  benzine,  benzol,  and  carbon  disulphide  and  on  the  con- 
trary immiscible  with  absolute  alcohol  and  glacial  acetic  acid.  On 
the  addition  of  HC1  and  furfurol  no  red  coloration  appeared.  The 
test  for  cotton-seed  oil  by  the  addition  of  sulphur  and  carbon  disul- 
phide gave  negative  results.  The  constants  were  ascertained  in  the 
usual  manner  and  found  as  follows : 


Specific  gravity  at  150  C   0.9125 

Acid  number   4.46 

Saponification  value    200.45 

Iodine  value  according  to  Hiibl  after  2  hours   69.9 

Iodine  value  according  to  Hiibl  after  6  hours   71.0 

Unsaponifiable  constituents    0.48  per  cent. 

Refractometer  number  in  a  Zeiss  butter-refractometer  at  250 .  59-60 

Optical  rotation  in  200  ccm.-tube   o 


The  oil  also  gave  the  reaction  for  elaidin.  Hehner's  method  for 
the  separation  of  the  fatty  acids  was  used  and  the  melting  point  of 
these  was  found  to  be  30.31  °,  the  congealing  point  22 0  and  the 
saponification  value  195.5.  The  fatty  acids  also  gave  an  iodine  value 
of  75.25.  After  recrystallization  from  alcohol  twice,  the  elaidic  acid 
showed  a  melting-point  of  51  °.  Experiments  on  mice  proved  this 
Ceje-Ol,  as  it  is  termed,  to  be  non-toxic.  Whether  it  will  be  of 
any  more  value  than  other  better-known  fatty  oils  in  the  treatment 
of  tuberculosis  remains  to  be  proven  clinically. 


Am.  Jour.  Pbarm.  ) 
January,  1914.  / 


Book  Reviews. 


45 


As  one  reads  through  this  volume,  depicting  the  work  done  at 
this  institute,  the  impression  is  gained  that  the  aim  of  the  workers  is 
the  scientific  one,  the  desire  for  the  truth;  the  truth  about  those 
remedies  for  which  there  may  be  a  legitimate  use  and  which  are 
more  or  less  ethically  introduced,  and  the  exposure  of  those  remedies 
which  are  secret  in  composition  and  for  which  extravagant  claims 
are  made.  John  K.  Thum. 

"  A  Hankbook  of  Useful  Drugs."  A  selected  list  of  important 
drugs  suggested  for  the  use  of  teachers  of  materia  medica  and 
therapeutics  and  to  serve  as  a  basis  for  the  examinations  by  state 
medical  examining  and  licensing  boards.  Prepared  under  the  direc- 
tion and  supervision  of  the  Council  on  Pharmacy  and  Chemistry  of 
the  American  Medical  Association.  Press  of  the  American  Medical 
Association,  535  North  Dearborn  Street,  Chicago,  1913. 

It  does  not  require  the  gifts  of  a  seer  or  the  abilities  of  a  prophet 
to  venture  the  opinion  that  this  rather  diminutive  volume  of  167 
pages  is  destined  in  the  near  future  to  have  a  decidedly  far-reaching 
influence  on  the  teaching  and  on  the  practice  of  therapeutics  and, 
consequently,  is  designed  to  have  an  equally  important  bearing  on 
the  future  development  of  pharmacy  and  the  efficiency  of  pharma- 
cists generally. 

Conscientious  students  of  medical  economics  have  long  appre- 
ciated the  waste  of  energy,  money  and  even  life  resulting  from  the 
haphazard  or  ignorant  misuse  of  drugs  and  medicines  so  general  a 
decade  or  more  since.  Some  nine  years  ago  the  Council  on  Phar- 
macy and  Chemistry  of  the  American  Medical  Association  made  its 
first  onslaught  on  quacks  and  quackery  in  the  medicine  supply  busi- 
ness and  although  the  Council  at  that  time  had  fair  reason  to  be- 
lieve that  it  might  be  assisted  in  its  efforts  by  at  least  the  more 
progressive  of  professional  pharmacists,  this  expected  cooperation 
has  not  been  forthcoming,  in  this  country  at  least.  Medical  prac- 
titioners, largely  through  the  American  Medical  Association,  have 
been  compelled  to  stand  practically  alone  in  their  fight  against  the 
purely  commercial  spirit  in  the  practice  of  pharmacy  of  to-day.  The 
little  book  before  us  is  the  latest  step  in  this  warfare,  representing  as 
it  does  the  fundamentally  constructive  work  of  the  Council  on  Phar- 
macy and  Chemistry,  as  the  earlier  work  "  Propaganda  for  Reform  " 
represents  the  destructive  work  of  the  same  body,  and  the  now  well- 
known  book,  "  New  and  Non-official  Remedies  "  represents  a  com- 
pilation of  reasonably  good  material  that  is  offered  for  future  in- 


46 


Book  Reviews. 


f  Am.  Jour.  Pharm. 
\    January,  1914. 


elusion  in  the  recognized  materia  medica  of  conservative  medical 
practitioners. 

The  object  of  this,  the  latest  of  the  three  books  offered  by  the 
Council  on  Pharmacy  and  Chemistry  of  the  American  Medical  Asso- 
ciation, is  perhaps  best  shown  by  quoting  rather  liberally  from  the 
preface,  not  necessarily  exactly  but  rather  the  purport  of  the  state- 
ments made,  so  as  to  avoid  occasional  repetition  : 

"  Many  of  the  articles  in  the  Pharmacopoeia  and  in  the  National 
Formulary  are  worthless  or  superfluous.  The  repeated  efforts  that 
have  been  made  to  eliminate  at  least  the  more  useless  of  these 
articles  have  uniformly  encountered  the  assertion  that  the  articles 
objected  to  are  used  somewhere  by  some  one,  and  that  they  should, 
therefore,  be  officially  recognized  and  authoritatively  defined. 

"  For  a  number  of  years  men  active  in  the  work  of  the  Council 
on  Medical  Education  and  in  the  Confederation  of  State  Examining 
and  Licensing  Boards  have  been  trying  to  restrict  instruction  and 
examination  in  materia  medica  to  the  more  important  drugs.  These 
efforts  apparently  failed,  so  far  as  the  Committee  of  Revision  of  the 
U.  S.  P.  is  concerned,  but  the  suggestions  have  been  taken  up  and 
elaborated  by  the  Council  on  Pharmacy  and  Chemistry  and  the  result 
is  this  volume  on  useful  drugs. 

"  The  book  is  offered  as  a  fundamental  list  of  drugs  and  prepara- 
tions with  which  all  medical  students  and  practitioners  might  be 
expected  to  be  familiar,  and  to  which,  therefore,  state  examining  and 
licensing  boards  might  largely  or  entirely  confine  their  examinations 
in  materia  medica.  As  it  now  stands,  it  embodies  a  total  of  about 
455  headings  including  265  titles  of  drugs  and  chemicals,  137  phar- 
maceutical preparations,  13  cross  references  and  40  general  defi- 
nitions or  descriptions  of  forms  of  medicines." 

It  is  confidently  predicted  that  an  intelligent  and  critical  use  of 
these  selected  drugs  will  prove  their  general  sufficiency,  and  show 
definitely  that  many  drugs  now  discussed  in  text  books  and  official- 
ized in  pharmacopoeias,  are,  to  say  the  least,  superfluous.  A  careful 
study  of  this  book  is  also  well  designed  to  demonstrate  that  many 
newly  discovered  or  widely  exploited  proprietary  preparations  have 
no  appreciable  advantage  over  established  drugs  and  preparations 
whose  limitations  and  possible  untoward  results  are  generally  well 
known. 

Pharmacists  and  teachers  of  pharmacy  should  acquaint  them- 
selves with  the  nature  as  well  as  the  intent  of  the  volume.  The  last 
word  on  a  limited  list  of  useful  drugs  has  not  as  yet  been  said,  but 


Am.  Jour.  Pharm.  \ 
January,  1914.  / 


Book  Reviews. 


47 


the  agitation  will  undoubtedly  do  much  toward  insuring  a  more 
uniform  and  better  supply  of  recognized,  standard  drugs,  by  placing 
responsibility  for  the  identity  and  purity  of  drugs  and  preparations 
on  the  dispensing  pharmacist,  where  it  rightly  belongs.  By  ulti- 
mately restricting  the  number  of  drugs  and  preparations  used  it 
will  be  possible  to  provide  adequate  supervision  of  the  medicines  dis- 
pensed ;  and  thus  the  pharmacist  will  eventually  come  to  occupy  the 
place  he  rightly  deserves  as  an  important  factor  in  safeguarding 
public  health.  M.  I.  W. 

War  Department:  Office  of  the  Surgeon  General,  Bulletin 
No.  3.  Studies  of  Syphilis.  By  Charles  F.  Craig,  Captain,  Medical 
Corps,  U.  S.  Army,  and  Henry  J.  Nichols,  Captain,  Medical  Corps, 
U.  S.  Army,  with  introduction  by  Major  Frederick  F.  Russell, 
Medical  Corps,  U.  S.  Army. 

This  Bulletin,  published  for  the  information  of  medical  officers 
by  authority  of  the  act  of  Congress  approved  August  23,  191 2,  and 
with  the  approval  of  the  Secretary  of  War,  is  striking  evidence  of 
the  fact  that  the  wonderful  advances  made  in  the  last  decade  for  the 
diagnosis  and  treatment  of  syphilis  are  being  made  use  of  and  appre- 
ciated by  the  medical  men  of  the  army.  In  no  branch  of  medicine 
has  more  rapid  progress  been  made.  And,  as  pointed  out  in  the 
introduction,  "  it  is  noteworthy  that  medicine  is  indebted  to*  lab- 
.  oratory  workers  and  research  institutions,  and  not  to  the  practical 
syphilographers,  for  this  phenomenal  progress." 

Exclusive  of  the  introduction  the  Bulletin  consists  of  a  series  of 
seven  papers  commencing  with  a  study  of  the  Spirochceta  pallida, 
its  morphology  and  cultivation.  Under  the  head  of  immunity  the 
interesting  statement  is  brought  out  that  there  is  no  true  immunity 
following  an  infection  from  this  parasite.  A  person  once  infected 
and  cured  can  be  reinfected.  Opinions  contrary  to  this  were  long 
held  by  the  medical  profession. 

The  diagnosis  of  syphilis  by  the  complement  fixation  test,  or 
Wassermann  test,  as  it  is  more  generally  known,  is  gone  into  very 
fully.  That  this  test  has  proven  of  great  value  in  .the  army  for 
diagnosis  and  control  over  treatment  is  attested  by  the  experience 
gained  from  the  performance  of  12,000  reactions. 

Ehrlich's  great  discovery,  salvarsan  and  neosalvarsan,  naturally, 
have  been  used  and  the  behavior  of  these  arsenic  combinations  with 
the  benzol  ring,  in  the  treatment  of  syphilis  is  very  fully  gone  into. 
The  superiority  of  these  drugs  over  mercury  as  a  specific  is  clearly 


48 


Book  Reviews. 


iAm.  Jour.  Pharm. 
January,  1914. 


proven;  yet,  in  the  light  of  our  present  knowledge,  the  consensus 
of  opinion  is  that  a  wise  combination  of  mercury  plus  salvarsan  or 
neosalvarsan  intravenously  procures  the  best  results. 

The  work  recorded  in  this  Bulletin  clearly  emphasizes  the  fact 
that  the  Medical  Corps  of  the  Army,  in  its  care  of  our  fighting  men, 
possesses  unusual  facilities  for  the  scientific  observation,  study,  and 
treatment  of  .this  disease.  John  K.  Thum. 

Essentials  of  Prescription  Writing.  By  Cary  Eggleston, 
M.D.,  Instructor  in  Pharmacology,  Cornell  University  Medical 
College,  New  York  City.  W.  B.  Saunders  Company,  Philadelphia 
and  London. 

Within  the  confines  of  this  small  volume  which  consists  of  only 
115  pages,  a  medical  student  or  graduate  physician  may  find  all 
the  information  necessary  to  equip  himself  in  the  principles  of 
prescription  writing,  a  branch  of  medicine  in  which  most  graduates 
in  medicine  find  themselves  utterly  at  sea  when  first  starting  prac- 
tice. Some  overcome  this  handicap  and  some  do  not;  to  the  latter 
we  most  heartily  recommend  this  handy  little  book,  although,  as  a 
matter  of  fact,  it  may  be  read  with  profit  by  all  who  practise 
medicine. 

This  book  consists  of  ten  chapters  which  embody  the  funda- 
mentals in  a  sequential  manner ;  the  chapter  devoted  to  Latin  gram- 
mar is  brief  but  thorough — the  author  has  evidently  learned  the  art 
of  saying  much  in  few  words — while  the  suggestions  offered  as  to 
flavoring,  coloring,  and  vehicles  (aqueous,  hydro-alcoholic  and  alco- 
holic), if  carefully  studied  and  faithfully  carried  out  by  physicians, 
would  soon  result  in  diminishing,  if  not  abolishing,  the  proprietary 
medicine  evil.  John  K.  Thum. 

Genealogy  of  the  Descendants  of  Thomas  French,  with 
Some  Account  of  Colonial  Manners  and  Doings,  together  with  One 
Hundred  and  Fifty  Picture  Prints  Compiled  and  Published  by 
Howard  Barclay  French,  of  the  Seventh  Generation.  Vol.  II,  Phila- 
delphia.   Privately  printed,  1913. 

Oliver  Wendell  Holmes  once  wrote  that  "  Philadelphia  was  the 
center  of  genealogy."  With  this  new  contribution  which  is  now 
completed,  Dr.  Holmes'  views  are  confirmed.  A  very  extended  re- 
view of  the  first  volume  was  given  in  this  Journal  in  June,  1909, 
p.  309.  The  work  is  handsomely  gotten  out  and  will  stand  as  a 
monument  to  Mr.  French. 


THE  AMERICAN 


JOURNAL  OF  PHARMACY 


This  is  an  American  plant,  which  has  run  wild  all  over  India. 
It  may  easily  be  known  by  its  glaucous,  prickly,  thistle-like  leaves, 
bright  yellow  flowers,  and  milky  juice.  The  latter  is  used  as  an 
application  to  ulcers  and  in  combination  with  the  juice  of  Aristo- 
lochia  bracteata  is  given  internally  in  syphilis  and  gonorrhoea.  In 
the  Concan  the  juice  with  milk  is  given  in  leprosy.  The  seeds  and 
oil  have  been  used  by  European  physicians.  The  oil  in  doses  from 
30  to  60  drops  is  a  valuable  remedy  in  dysentery  and  other  affections 
of  the  internal  canal.  Fluckiger  found  4  to  5  gms.  to  have  a  mild 
purgative  effect.  An  extract  made  from  the  whole  plant  has  been 
found  to  have  an  aperient  action  and  the  milky  juice  to  promote  the 
healing  of  indolent  ulcers. 

The  oil  used  for  examination  was  obtained  by  pressing  the 
crushed  seeds  in  a  screw  press  in  the  laboratory  in  presence  of  the 
author.    The  chances  of  adulteration  were  thus  avoided. 


Some  of  the  crushed  seeds  were  submitted  to  steam  distillation; 
the  distillate  had  a  slight  opalescence  and  a  very  pungent  odor,  but 
no  oil  came  over. 

47.1176  gms.  of  the  crushed  seeds  were  exhausted  in  a  Soxhlet 
apparatus  with  petroleum  ether,  the  latter  evaporated  off  when 
10.4966  gms.  of  a  thin  brown  colored  oil  was  left  behind.  Hence 
the  percentage  of  oil  is  22.3.  According  to  Charbonnier  the  seeds 
contain  36  per  cent,  of  oil. 

The  petroleum  ether  extract  has  a  pale  greenish-yellow  color 
with  a  green  fluorescence,  if  it  be  evaporated  at  the  ordinary  tem- 
perature, the  oil  left  behind  has  an  olive  green  color.    If  this  be 


THE  OIL  OF  ARGEMOtf  E  MEXICAN  A. 

By  Kshitibhushan  Bhaduri,  M.Sc^  OFFlC^- 


FEBRUARY,  1914 


Historical. 


Experimental. 


(49) 


The  Oil  of  Argemone  Mexicana. 


Am.  Jour.  Pharm. 
February,  1914.. 


either  left  exposed  to  the  atmosphere  or  heated  on  the  water  bath  it 
gradually  acquires  a  rich  brown  color.  If  it  be  still  further  heated 
the  color  deepens  and  it  diffuses  a  very  intense  odor,  like  that  of 
the  juice  of  the  fresh  plant. 

The  pressed  oil  was  of  a  deep  brown  color,  had  a  mild  odor  and 
was  tasteless.  The  freshly  obtained  oil  was  very  thin,  but  on  keep- 
ing it  gradually  thickened.  Crossley  and  Le  Sueur  (Journ.  Soc. 
Chem.  Ind.}  1898,  991)  say  the  fresh  oil  is  of  orange  color  and  has  a 
slight  but  distinctive  smell. 

The  mixed  fatty  acids  had  a  paler  color  and  were  very  thin. 

The  oil  on  keeping  exposed  to  the  atmosphere  or  on  treatment 
with  an  oxidizing  agent  deposited  a  very  small  quantity  of  a  red 
crystalline  substance  (M.P.  1720  C). 

The  oil  gradually  thickened  with  the  lowering  of  temperature, 
until  at  1 70  C.  the  clear  liquid  became  turbid,  the  temperature  re- 
mained constant  for  a  little  time  at  160  C.  Charbonnier's  oil  re- 
mained clear  at  — 8°  C.  and  Fluckiger's  oil  at  — 6°  C. 

The  specific  gravity  was  determined  at  two  different  temperatures, 
at  28 0  C.  and  at  the  boiling  point  of  water.  In  the  former  case  it 
was  0.91 17  and  at  the  latter  it  was  0.9007.  Charbonnier  obtained  a 
specific  gravity  of  0.920,  Fluckiger  0.919  at  16.5 0  C.  and  Crossley 
and  Le  Sueur  0.9247-0.9259  at  1 5.50  C. 

The  refractive  index  obtained  with  a  Pulfrich's  refractometer 
was  430  34'  at  32 0  C.  or  1.46552.  With  a  butyro  refractometer 
Crossley  and  Le  Sueur  obtained  at  400  C.  a  refractive  index  of  62.5. 

The  oil  and  absolute  alcohol  were  miscible  in  any  extent.  For 
the  determination  of  its  solubility  in  dilute  alcohol  the  following 
method  was  adopted.  In  a  stoppered  graduated  tall  cylinder  a 
measured  volume  of  oil  was  introduced,  to  this  a  known  volume  of 
alcohol  was  added  and  then  water  added  drop  by  drop  with  con- 
tinuous shaking  till  a  permanent  turbidity  was  obtained.  The  total 
volume  was  read  off  and  from  this  when  the  volume  of  oil  and 
alcohol  was  subtracted  the  volume  of  water  added  was  obtained. 

Table  of  Solubility  in  Alcohol  of  Different  Strength  at  32°C. 


Oil. 


Water. 


Alcohol. 


10 
10 
IO 
IO 
II 


22 


28 
24 
24 


9 
15 


12 
20 
32 
42 
42 
45 


AFeb£la^  VmT' }      The  Oil  of  Argemone  Mexicana.  51 

116.4  c.c.  oi~  alcoholic  potash  (calculated)  were  required  for 

the  saponification  of  3.4828  gms.  of  oil;  hence  the  saponification 
value  is  185.5.  The  saponification  obtained  by  Crossley  and  Le  Sueur 
is  187.8-190.3. 

The  oil  was  acetylated  by  boiling  with  acetic  anhydride  and 
purified,  then  dried  with  anhydrous  Sodium  Sulphate.   3.23  gms.  of 

oil  thus  obtained  required  122  c.c.  (calculated)  of       potash  for 

complete  saponification.  The  saponification  value  of  the  acetylated 
oil  was  213.4  and  deducting  from  this  185.5,  the  saponification  value, 
we  got  27.9  as  the  acetyl  value. 

The  oil  contained  a  large  proportion  of  free  fatty  acid  for  which 
determination  3.5998  gms.  of  oil  was  dissolved  in  50  c.c.  of  neutral- 
ized alcohol  and  a  little  phenolphthalein  solution  added  and  titrated 

with  -j^  alkali.    It  was  found  that  94.3  c.c.  was  necessary  for 

neutralization,  hence  the  acid  value  is  146.  Two  specimens  of  oil 
were  examined  by  Crossley  and  Lie  Sueur  who  found  6.0  and  83.9 
as  the  acid  value. 

In  the  aqueous  solution  left  after  the  decomposition  of  the  soap 
with  an  acid,  the  presence  of  the  following  fatty  acids  was  proved 
(1)  acetic  acid  proved  by  the  Cacodyl  test  and  (2)  valeric  acid  by 
the  formation  of  the  ester. 

In  a  weighed  flask  2.3696  gms.  of  oil  was  taken  and  dissolved  in 
50  c.c.  of  chloroform,  and  Bromine  gradually  added  till  no  further 
absorption  took  place.  It  was  then  evaporated  off  on  the  water  bath 
and  dried.  The  weight  of  the  brominated  oil  now  was  4.7912  or 
the  increase  in  weight  was  102.2  per  cent.   This  is  the  bromine  value. 

The  iodine  value  of  the  oil  is  106.7.  That  obtained  by  Crossley 
and  Le  Sueur  is  119,91-122.5. 

2.7  gms.  of  oil  was  saponified,  then  decomposed  with  dilute 

sulphuric  acid  and  submitted  to  steam  distillation.    0.33  c.c.  ©f-^ 

alkali  was  required  for  neutralization  of  100  c.c.  distillate.  There- 
fore the  Reichert-Meisel  value  is  0.61. 

From  1.8426  gms.  of  oil  the  author  obtained  1.7295  gms.  of  a 
mixture  of  insoluble  fatty  acids  and  unsaponifiable  matters.  The 
Hehner's  value  is  94.02.   The  above  authors  obtained  95.07. 

The  glycerol  was  estimated  by  the  Benedikt  and  Zsismondy 
process.    This  consists  in  oxidizing  the  glycerol  to  oxalic  acid  by 


52  The  Oil  of  Argemone  Mexicana.      {A^b^ary  "191?" 

potassium  permanganate.  From  the  amount  of  oxalic  acid  obtained 
the  weight  of  glycerol  was  calculated.  It  was  found  to  be  15.48 
per  cent. 

6.1996  gms.  of  oil  was  saponified,  alcohol  evaporated  off;  it 
was  then  dissolved  in  water  and  extracted  with  ether.  The  ethereal 
extract  on  evaporation  left  behind  .1418  gm.  of  residue  or  the  oil 
contains  2.29  per  cent,  of  unsaponifiable  matter. 

The  elaidin  produced  by  the  oil  was  an  orange-colored,  dough-like 
mass.    The  reaction  was  very  violent. 

When  sulphur  chloride  was  added  to  a  solution  of  equal  volume 
of  oil  and  carbon  disulphide  a  violent  reaction  ensued,  the  whole 
mass  frothing  up;  a  very  sticky  mass  was  left  behind. 

When  10  gms.  of  sulphuric  acid  was  added  to  50  gms.  of  oil  the 
rise  of  temperature  was  65 0  C.    The  Maumene  test  was  65 0  C. 

The  rise  in  temperature  on  brominating  1  c.c.  of  oil  was  16.5 0  C. 

The  oil  gave  no  characteristic  color  reaction  with  sulphuric  acid 
even  when  it  was  diluted  with  carbon  disulphide.  The  color  was 
blackish-brown  in  the  former  case  and  in  the  latter  case  light  brown. 

On  shaking  the  oil  with  nitric  acid  it  acquired  a  deep  brown 
color  and  the  acid  a  deep  red  color.  On  heating  it  a  violent  reaction 
ensued,  a  pale  orange-colored  scum  was  formed  when  the  whole  was 
allowed  to  stand  over  night. 

For  the  determination  of  oxygen  absorption  power  a  quantity 
of  lead  was  prepared  by  Livache's  method ;  about  a  gram  of  it  was 
spread  upon  a  watch  glass  and  a  weighed  volume  of  the  oil  was 
spread  on  it  by  allowing  it  to  drop  on  different  places.  This  was 
weighed.  The  weights  on  each  successive  day  were  noted  till  there 
was  no  further  increase  in  weight. 


Gain  in  Weight  of  1.3437  gms.  of  Oil. 


Days. 

Increase  in  weight. 

Per  cent,  increase. 

1st  day. 

O.269 

2  .002 

2nd  day. 

O.  107 

O.8 

3rd  day. 

O . OO84 

O.6 

5th  day. 

O.OI52 

I  .  I 

6th  day, 

O.OO59 

O.44 

8th  day. 

O . OO65 

O.48 

9th  day. 

O.OOI5 

O.  I 

10th  day. 

No  increase. 

Total  gain  in  weight  till  constant  =  5.522. 


AreWJuTy)7oi4m'}      The  0il  °f  Argemone  Mexicana.  53 

39  c.c.  of  the  oil  was  fractionally  distilled  at  15  mm.  pressure 
when  the  following  fractions  were  obtained. 


Temperature. 


2i5°-2i7°C. 

2I7°-224°  C. 
224°-228°  C. 

228°-23I°C. 

23i°-235°  C. 


Weight  of  fraction. 


3-8i 
9.08 
9.24 

6-45 
2.79 


Remarks. 


Instantly  solidified. 

Solidified  but  contained  some  liquid. 

Liquid,  on  prolonged  keeping  a  few  crystals 

separated  out. 
Pale  brown  liquid. 
Greenish  liquid. 


Examination  of  the  Mixed  Fatty  Acids. 

The  specific  gravity  at  28 0  C.  is  0.9065  and  at  the  boiling  point 
of  water  0.8889. 

2.0688  gms.  required  for  saponification  90.4  c.c.  of  alkali. 

The  saponification  value  is  194. 

0.40745  gms.  of  oil  absorbed  0.6003  gms.  of  iodine  from  a 
solution  of  iodine  and  mercury  bichloride  in  absolute  alcohol.  The 
iodine  value  hence  is  147.4. 

To  find  out  the  neutralization  value,  3.6638  gms.  of  the  mixture 
were  diluted  with  50  c.c.  of  neutralized  alcohol,  a  drop  of  phenol- 
phthalein  solution  added  and  titrated  with  a  normal  solution  of 
caustic  potash.  It  was  found  12.64  c-c-  were  necessary  for  this 
purpose.  Hence  it  follows  that  193.2  mgms.  of  KOH  were  necessary 
for  the  neutralization  of  one  gram  of  the  mixture.  The  mean 
molecular  weight  is  found  by  dividing  56.1  by  that  found  necessary 
for  the  neutralization  of  one  gm.  of  oil. 

Let  M  be  the  molecular  weight  and  n  the  weight  of  KOH  in  gms. 

n 

now  n  =  a  X  0.0561  (a  number  of  c.c.'s  of  riormal  KOH). 

 ^1__=  jooo  _  jooo >  8 

a  X  0.0561  a  3.45 

3-33°3  gms.  of  oil  gave  2.5847  gms.  of  liquid  fatty  acid  by  the 
lead-salt-ether  process.  Therefore,  77  per  cent,  of  the  total  fatty 
acid  was  liquid  fatty  acid. 

It  was  found  that  the  oil  did  not  contain  any  stearic  acid. 

The  lactone  value  of  the  mixed  fatty  acid  was  the  difference 
between  the  saponification  and  neutralization  values,  .8. 


54  Assay  Process  for  Quinine  in  Tablets.  { A™eb/uary  Pi9iF' 

The  titer  test  of  temperature  of  turbidity  of  the  mixed  fatty  acid 
is  22°  C. 

The  mixed  fatty  acid  contains  8.14  per  cent,  of  lauric  acid  as  was 
found  by  fractional  distillation  of  the  oil  in  vacuo. 

Chemical  Laboratory,  Presedency  College,  Calcutta. 


AN  ASSAY  PROCESS  FOR  QUININE  IN  TABLETS. 
By  Sidney  F.  Fieselmann,  Peoria,  111. 

A  rapid  method  for  the  quantitative  estimation  of  quinine  in 
tablets,  containing  no  other  chloroform  soluble  constituents,  that  are 
not  expelled  at  a  temperature  of  1250  C,  which  has  been  successfully 
used  by  the  author  with  accurate  results,  is  the  following : 

Count  out  a  sufficient  number  of  tablets,  so  as  to  make  the  total 
number  represent  10  grains  of  quinine  or  quinine  salts,  based  on 
the  quantity  claimed  on  the  label.  If  the  quantity  stated  per  tablet 
cannot  be  made  to  come  out  in  a  whole  number  of  tablets,  take  the 
number  of  tablets,  which  contain  about  10  grains  and  make  the 
required  correction.  Weigh  the  tablets  counted  out  accurately  on  an 
analytical  balance.  Multiply  this  weight  by  two  and  call  it  X  grams. 
Then  powder  a  sufficient  amount  of  tablets  and  force  all  through  a 
number  sixty  sieve.  In  case  of  coated  tablets  be  careful  not  to 
loose  any  particle  of  the  hard  coating  or  parts  of  tablets  during  the 
process  of  powdering  and  sifting.  Then  mix  thoroughly  after  this 
operation,  so  as  to  insure  a  uniform  representative  mixture. 
Weigh  up  X  grams  of  this  powder  in  a  100  c.c.  Erlenmeyer 
flask,  add  50  c.c.  of  chloroform,  accurately  measured,  stopper 
and  shake  well.  Now  add  5  c.c.  of  ammonia  water  U.  S.  P., 
stopper  well  and  shake  thoroughly  for  20  minutes.  Let  stand  for 
about  12  hours  in  a  cool  place,  with  occasional  shaking,  and  decant 
the  chloroform  into  a  separatory  funnel,  stopper  well  and  allow  to 
stand  until  separation  takes  place.  Take  a  5  cm.  plain  folded  filter 
paper,  on  a  small  60 0  glass  funnel,  moisten  with  a  little  chloroform, 
taking  care  not  to  have  any  chloroform  drop  into  the  measuring 
cylinder  or  any  remaining  in  the  tube  of  the  funnel.  Then  withdraw 
enough  of  the  chloroformic  solution  in  the  separating  funnel  and 
filter  the  same  through  the  moistened  filter  paper  into  a  50  c.c. 
measuring  cylinder  until  25  c.c.  are  obtained. 


^'bra^iy  Pi9ai4m' }  Assay  Process  for  Quinine  in  Tablets.  55 

If  this  25  c.c.  of  filtrate  is  colorless  or  of  a  light  straw  color, 
transfer  it  to  a  tared  beaker  of  60-100  c.c.  capacity,  rinsing  the 
cylinder  with  three  portions  of  10  c.c.  of  chloroform  and  adding  the 
same  to  the  chloroform  solution  in  the  tared  beaker.  Then  evapo- 
rate the  chloroform  carefully  on  a  water  bath.  If  the  filtrate  is  highly 
colored,  from  the  coating,  coloring  matter,  or  resinous  substances  in 
the  tablets,  transfer  the  same  into  a  clean  separatory  funnel,  rinse 
out  the  cylinder  as  before,  adding  the  same  to  the  chloroform 
solution  in  the  separatory  funnel,  and  shake  out  with  three  portions 
of  normal  sulphuric  acid,  15,  5,  5  c.c.  respectively,  each  portion 
diluted  with  5  c.c.  of  distilled  water.  Collect  the  combined  acid 
aqueous  solution  in  a  clean  separatory  funnel,  add  a  small  piece  of 
red  litmus  paper,  make  distinctly  alkaline  with  ammonia  water 
U.  S.  P.  and  shake  out  with  three  successive  portions  of  25,  15,  and 
15  c.c.  of  chloroform,  collecting  the  same  in  a  tared  beaker.  After 
the  chloroform  has  evaporated,  redissolve  the  residue  in  5  or  10  c.c. 
of  ether  and  let  evaporate  spontaneously. 

Finally,  place  the  tared  beaker,  containing  the  quinine  residue  in 
a  drying  oven  and  heat  to  a  constant  weight  at  1250  C,  cooling  the 
tared  beaker  each  time  in  a  desiccator  before  weighing.  It  usually 
requires  from  one  to  three  hours  of  heating  until  the  weight  is  con- 
stant. The  tared  beaker  should  be  chemically  clean  and  heated  for 
at  least  one  half  hour  at  125 0  C.  and  cooled  in  a  calcium  chloride 
desiccator,  before  it  is  weighed  and  the  chloroformic  solution  added. 

If  exactly  10  grains  of  quinine  or  the  salts  of  quinine  were  taken 
as  per  label  the  residue  should  weigh  the  following : 


For  Quinine  Alkaloid  U.  S.  P.  (Quinine  +  3H00)   0.5553  Grams. 

For  Quinine  Bisulphate  U.  S.  P   0.3830  Grams. 

For  Quinine  Hydrobromide  U.  S.  P   0.4963  Grams. 

For  Quinine  Hydrochloride  U.  S.  P   0.5296  Grams. 

For  Quinine  Salicylate  U.  S.  P   0.4457  Grams. 

For  Quinine  Sulphate  U.  S.  P   0.4814  Grams. 


Tablets  containing  substances  like  calcined  magnesia  as  a  drying 
agent,  do  not  filter  rapidly  by  the  above  method.  The  water  in  the 
ammonia  water  forms  a  gelatinous  mass  with  the  magnesia,  which 
prevents  rapid  filtration  and  sometimes  stops  it  altogether.  In  that 
case  the  following  method  is  suggested.  Measure  out  in  a  50  c.c. 
measuring  cylinder,  5  c.c.  of  spirit  of  ammonia  U.  S.  P.,  add  a 
sufficient  quantity  of  chloroform  to  make  exactly  50  c.c.  Use 


56 


U.  S.  P.  ipoo  Menstrua. 


{Am.  Jour.  Piiarm. 
February,  1914. 


this  as  a  menstruum  and  follow  the  other  directions  as  given 
above  omitting  the  ammonia  water.  This  last  method  cannot 
always  be  used  on  account  of  the  alcohol  in  the  spirit  of  ammonia 
U.  S.  P.,  which  dissolves  more  substances  than  the  chloroform  would 
alone  and  so  the  residue  would  not  be  pure  quinine.  On  the  other 
hand  chloroform  alone  will  not  dissolve  anything  but  the  quinine  of 
the  substances  usually  found  in  quinine  tablets. 

In  order  to  obtain  sufficient  chloroformic  filtrate  from  tablets 
containing  an  unusual  large  quantity  of  other  material  and  only 
a  small  amount  of  quinine,  it  may  be  necessary  to  increase  the 
chloroformic  menstruum  from  50  c.c.  to  100  c.c.  or  more,  filtering 
off  one  half  the  quantity  used,  following  the  instructions  given 
above. 

Sutliff  and  Case  Co.,  Peoria,  111. 


U.  S.  P.  1900  MENSTRUA. 
By  H.  C.  Hamilton. 

It  seems  almost  superfluous  to  call  attention,  at  this  late  date,  to 
certain  points  in  the  8th  Revision  of  the  U.  S.  P.  which  need  correc- 
tion in  the  forthcoming  9th  Revision.  Particularly  does  it  seem 
unnecessary  in  view  of  the  fact  that  the  objectionable  features  to 
which  this  article  alludes  have  been  pointed  out  before  and  by  several 
critics.  The  excuse  for  doing  so,  however,  if  any  is  necessary,  is 
that  the  data  here  published  may  be  of  value  to  those  who  have  under 
consideration  for  the  9th  Revision  of  the  Pharmacopoeia  the  menstrua 
for  the  extraction  of  the  digitalis  series  of  heart  tonics.  The  menstrua 
to  which  we  refer  are  for  the  preparation  of :  I.  F.  E.  Digitalis ; 
II.  F.  E.  Squill ;  III.  F.  E.  Convallaria. 

I.  The  first  two  of  these  were  referred  to  by  Houghton  and 
Hamilton  1  in  the  following  words : 

"  3.  Fluidextract  digitalis,  U.  S.  P.  8th  Rev.,  48  per  cent,  alcohol. 

"  Average  potency  of  eleven  samples  at  time  of  manufacture 
55  H.  T.  U.  per  c.c.  Three  and  a  half  years  later  35  H.  T.  U.  Aver- 
age loss  about  10  per  cent,  yearly. 

"  A  very  important  point  should  be  noted  in  this  connection ; 
namely,  the  menstruum  adopted  in  the  last  U.  S.  P.  for  the  prepara- 
tion of  fluidextract  digitalis  is  much  less  desirable  than  the  U.  S.  P. 
7th  Revision  in  at  least  two  respects.   Repeated  trials  show  that  it  is 


Am.  Jour.  Pharm. ) 
February,  1914.  j" 


U.  S.  P.  1900  Menstrua. 


57 


almost  impossible  to  get  a  finished  product  containing  the  full  number 
of  H.  T.  U.  of  the  standard  we  had  previously  adopted,  the  average 
being  as  above  stated,  55  H.  T.  U.  per  c.c,  while  with  drug  of  the 
same  quality  when  the  7th  Revision  menstruum  is  employed  no  diffi- 
culty is  experienced.  Owing  to  this  it  was  decided  to  no  longer 
attempt  to  assay  physiologically  the  8th  Revision  product  and  to 
take  such  statement  referring  to  it  off  the  label,  but,  in  order  to 
supply  the  medical  profession  with  a  full  strength  fluidextract  of  the 
drug,  it  was  decided  to  prepare  such  with  a  menstruum  containing 
a  larger  per  cent,  of  alcohol  which  could  be  assayed  and  so  labelled. 
In  the  second  place  the  loss  in  potency  of  the  8th  Revision  is  about 
10  per  cent,  per  year,  while  with  the  7th  Revision  it  is  less  than 
one-half  as  great,  or  about  4  per  cent.  The  results  coincide  quite 
closely  with  those  following  the  change  made  in  the  menstruum  for 
the  fluidextract  of  squill  except  that  the  loss  in  activity  was  greater 
in  the  latter  drug,  as  pointed  out  by  Houghton  2  three  years  ago.  In 
this  paper  several  methods  of  physiological  assay  showed  very 
clearly  that  a  serious  mistake  had  been  made  in  changing  to  acetic 
acid  as  a  menstruum.  The  writers  feel  certain  that  any  one  who  has 
tried  the  8th  Revision  menstruum  for  fluidextract  digitalis  has  found 
that  it  is  much  less  satisfactory  from  a  pharmaceutical  point  of  view, 
to  say  nothing  of  the  loss  in  potency." 

To  this  we  wish  to  add  data  since  obtained  on  F.  E.  Digitalis  as 
follows : 


The  above  samples  were  prepared  from  one  lot  of  drug,  using  100 
grams  and  extracting  until  exhausted. 

Another  small  sample  of  drug  carefully  extracted  by  both 
methods  and  tested  gave  results  as  follows : 


A  sample  of  drug  extracted  with  several  strengths  of  alcohol  gave 
the  following  results : 


Menstruum. 
50  per  cent,  alcohol . 
80  per  cent,  alcohol 


Per  cent.  Activity. 


IOO 


120 


with  50  per  cent,  alcohol 
with  80  per  cent,  alcohol 


no  per  cent,  of  standard. 
140  per  cent,  of  standard. 


Menstruum. 


Per  cent.  Activity. 


94  per  cent,  alcohol 
75  per  cent,  alcohol., 
62.7  per  cent,  alcohol. 
50    per  cent,  alcohol. 


90 
140 
125 


no 


5« 


U.  S.  P.  ipoo  Menstrua. 


f  Am.  Jour.  Pharm. 
\   February,  1914. 


The  following  table  shows  the  tests  of  commercial  lots  of  F.  E. 
Digitalis,  U.  S.  P.  8th  Rev.  (a)  before  and  (b)  after  an  attempt 
to  improve  the  quality  by  concentrating  the  extract. 


Number. 

Tested. 

Per  cent.  Activity. 

I  (a) 

8/4/9 

8=? 

i  (b) 

8/19/9 

go 

2  (a) 

7/20/9 

85 

2  (b) 

8/4/9 

85 

3  (a) 

3/4/9 

60 

3  W 

4/2/9 

100 

4  (a) 

I/3I/8 

80 

4  (b) 

2/8/8 

80 

5  W 

5/23/7 

75 

5  (b) 

6/1/7 

83 

Further  data  on  20  samples  of  the  preparation  show  results  of 
first  tests  ranging  from  50  to  100  per  cent,  standard  and  averaging 
exactly  78  per  cent. 

The  standard  referred  to  is  the  average  activity  obtained  from 
12  lots  of  crude  drug,  botanically  of  first  class  quality,  selected  at 
random  and  extracted  with  62.7  per  cent,  alcohol,  the  official  men- 
struum of  the  U.  S.  P.  7th  Revision.  The  activity  was  determined 
by  the  frog  method  described  by  Houghton  3  as  a  means  of  standard- 
izing the  heart  tonics  of  the  digitalis  series.  In  that  article  attention 
was  called  to  the  enormous  variation  in  samples  of  the  crude  drug  for 
sale  on  the  open  market. 

The  value  of  such  a  method  is  also  shown  when  endeavoring 
to  extract  from  active  material  all  the  therapeutically  active  sub- 
stances and  to  establish  by  experiments  on  other  than  the  human 
subject  the  relative  activity  of  extracts  obtained  by  means  of  various 
menstrua. 

The  above  results  speak  for  themselves,  but  if  additional  authority 
is  needed  it  should  be  sufficient  to  note  that  the  menstrua  for  making 
tinctures  and  fluidextracts  of  digitalis  in  the  official  Pharmacopceise 
of  the  world,  specify,  almost  without  exception,  a  percentage  of 
alcohol  in  excess  of  that  official  in  the  U.  S.  P.  8th  Revision.  The 
menstruum  adopted  in  1906  by  the  Brussels  Conference  is  70  per  cent, 
alcohol  and  it  is  to  be  hoped  that  the  Revision  Committee  will  be 
influenced  by  this  in  adopting  an  official  menstruum  for  the  9th 
Rev.  of  the  U.  S.  P. 

II.  As  noted  before  in  the  abstract  from:  the  American  Journal 


Am.  Jour.  Pharm.  \ 
February,  1914.  / 


U.  S.  P.  1900  Menstrua. 


59 


of  Pharmacy  1  a  mistake  was  certainly  made  in  adopting  for  the 
preparation  of  F.  E.  Squill,  U.  S.  P.,  8th  Rev.,  a  menstruum  com- 
posed of  a  10  per  cent,  solution  of  Acetic  Acid.  This  is  so  far  from 
being  ideal  for  extracting  the  active  substances  from  Squill  bulb  that 
it  is  practically  impossible  to  prepare  an  extract  representing  the 
activity  of  the  crude  drug. 

Comparison  of  the  activity  of  F.  E.  Squill,  U.  S.  P.,  1890  and  1900, 
was  made  by  Houghton  4  as  follows : 

"  Comparative  Strength  of  Fluid  Extract  of  Squill  Prepared  from 
the  Same  Lot  of  Drug  According  to  the  United  States  Pharmacopoeia 
of  1890  and  1900: 

"  1  U.S. P.,  1890,  140  per  cent,  as  active  as  standard  fluid  extract. 

"  2  U.S. P.,  1890,  140  per  cent,  as  active  as  standard  fluid  extract. 

"3  U.S. P.,  1900,  60  per  cent,  as  active  as  standard  fluid  extract. 

"4  U.S. P.,  1900,  60  per  cent,  as  active  as  standard  fluid  extract. 

"  It  may  be  observed  that  activity  of  both  products  is  high  as  com- 
pared with  the  results  given  in  Table  2.  This  probably  is  due  to 
the  great  care  exercised  completely  to  exhaust  the  drug  and  to  the 
high  quality  of  the  drug. 

"  In  order  to  meet  any  objections  that  might  be  offered  against 
the  results  as  shown  by  the  special  method  of  assay  employed,  the 
work  was  checked  by  experiments  on  dogs  showing  the  comparative 
activity  of  the  two  products  in  producing  changes  in  the  blood-pres- 
sure, which  is  perhaps  the  most  characteristic  physiologic  action  of 
the  members  of  the  digitalis  series/' 

The  results  of  the  latter  experiments  are  here  recorded  in  tabular 
form  for  more  convenient  reference. 

Experiment  I. 

F.  E.  Squill,  U.  S.  P.,  1890.         F.  E.  Squill,  U.  S.  P.,  1900. 
Before  After 
injection.  injection.  Before.  After. 

Pulse  Rate   100  96  116  138 

Blood-pressure    46  54  48  45 

In  this  experiment  0.3  c.c.  F.  E.  Squill,  U.  S.  P.,  1890,  was  injected 
at  10.45  A-M-  in*0  the  femoral  vein  of  an  anaesthetized  dog.  Then 
at  2.41  p.m.,  when  the  effect  of  the  first  injection  had  passed,  the 
same  amount  of  F.  E.  Squill,  U.  S.  P.,  1900,  was  injected. 

In  the  second  experiment  the  order  of  injection  was  reversed  an- 
other dog  being  used  for  the  test,  and  the  same  amount  of  each 
preparation  injected. 


6o 


U.  S.  P.  1900  Menstrua. 


f  Am.  Jour.  Pharm. 
(   February,  1914. 


Experiment  II. 


Pulse  Rate  . . . 
Blood-pressure 


F.  E.  Squill,  U.  S.  P.  ,  1900. 

Before.  After. 
. . .    102  I44 


F.  E.  Squill,  U.  S.  P.  ,1890. 


Before.  After. 
IOO  94 
52  50 


47  46 


Note. — In  both  cases  the  U.  S.  P.,  1900,  preparation  increased  the 
rate  and  lowered  the  pressure.  This  is  directly  opposite  in  effect 
from  the  characteristic  action  of  the  heart  tonics  in  general  and  from 
that  of  the  F.  E.  Squill,  U.  S.  P.,  1890,  from  the  same  drug. 

In  this  case  again  a  stronger  alcohol  is  better.  If  the  drug  is 
finely  ground  and  extracted  with  menstrua  containing  60  per  cent, 
or  less  of  alcohol,  it  swells  so  that  percolation  is  either  entirely  or 
almost  prevented.  It  becomes  necessary  either  to  cut  the  bulb  without 
grinding  or  toi  mix  with  sawdust  in  order  to  have  it  sufficiently  open 
to  percolate  properly.  An  additional  objection  is  in  the  large  amount 
of  gummy,  water-soluble  extractive  obtained  with  such  menstrua. 
A  fluid  extract  of  better  appearance,  better  keeping  quality  and  con- 
taining practically  all  the  available  activity  of  the  drug,  can  be 
obtained  by  the  use  of  80  per  cent,  alcohol.  Repeated  experiments 
have  shown  the  excellence  of  this  menstruum  over  that  of  the  7th  or 
8th  Revisions  of  the  U.  S.  P. 

III.  Fluid  Extract  Convallaria,  U.  S.  P.,  1900,  is  not  so  open 
to  criticism  as  the  others  but  the  menstruum  is  not  entirely  satis- 
factory. There  are  certain  advantages  to  be  gained  by  using  a 
stronger  alcoholic  menstruum  than  that  prescribed  in  the  8th  Revis- 
ion U.  S.  P.  While  these  advantages  are  more  apparent  when 
experiments  are  conducted  on  a  manufacturing  scale  than  when 
small  experimental  lots  of  fluid  extract  are  prepared,  even  in  the 
latter  case  the  advantages  are  very  real. 

Several  experiments  have  been  carried  out,  of  which  the  following 
is  used  as  an  example : 

A  small  lot  of  drug  was  divided  into  two  portions,  one  of  which 
was  extracted  as  prescribed  in  the  U.  S.  P. ;  namely,  with  62.7  per 
cent,  alcohol,  the  other  with  80  per  cent,  alcohol.  These  extracts  were 
carefully  concentrated  to  fluid  extract  volume  and  tested  for  activity 
by  the  method  previously  cited,  with  the  following  results : 


Menstruum. 

62  per  cent,  alcohol 
80  per  cent,  alcohol 


Per  cent.  Activity. 
IOO 
I20 


VebiJuTiT,Pih9T4m' }     Standardisation  of  Heart  Tonics.  61 

The  advantages  to  be  gained  from  using  a  stronger  alcoholic  men- 
struum for  extracting  cdnvallaria  roots  and  rhizome  are  not  merely 
the  greater  activity  obtainable,  but  in  the  improved  appearance  of 
the  extract  and  its  greater  stability.  It  contains  less  of  the  gummy 
extractives  and  more  alcohol,  both  of  which  are  desirable  features,  as 
they  affect  deterioration,  while  the  20  per  cent,  increase  in  activity 
from  the  use  of  80  per  cent,  alcohol  is  no  less  desirable. 

It  is  to  be  hoped  that  those  in  charge  of  revising  the  forthcoming 
U.  S.  Pharmacopoeia  will  consider  these  suggestions. 

LITERATURE  CITED. 

1  American  Journal  of  Pharmacy,  October,  1909. 

2  Jour.  American  Medical  Ass'n.,  June  12,  1906. 

3  Ibid.,  September  11,  1897. 

4  Ibid. ,  May  12,  1906. 

From  the  Research  Laboratory  of  Parke,  Davis  &  Co., 

Detroit,  Michigan. 


THE  PHYSIOLOGICAL  STANDARDIZATION  OF  THE 
HEART  TONICS.* 

By  Professor  William  A.  Pearson,  of  The  Hahnemann  Medical  College 

of  Philadelphia. 

"  The  Physiological  Testing  of  the  Heart  Tonics,"  which  is  the 
subject  assigned  for  my  discussion,  is  a  very  inaccurate  title. 

A  satisfactory  definition  of  a  tonic  has  never  been  given,  much 
less,  a  heart  tonic.  The  word  physiological  is  not  appropriate  be- 
cause when  any  active  drug  is  given  the  normal  processes  of  the  body 
are  no  longer  physiological. 

For  these  reasons,  such  a  subject  as  "  The  Pharmacologic  Stand- 
ardization of  Drugs  Having  a  Particular  Action  on  the  Heart  "  would 
be  far  more  fitting. 

Since  Digitalis  is  the  most  important  member  of  the  group  of 
drugs  known  as  "  heart  tonics,"  a  discussion  of  the  methods  of 
standardizing  this  drug  will  be  first  considered. 

Medicinal  Use  and  Therapeutic  Action  of  Digitalis, 
It  is  well  known  that  Digitalis  has  had  a  place  in  domestic  and 
medicinal  therapy  for  centuries,  and  many  of  you  know  that  a  Bir- 


*  A  special  lecture  given  at  The  Philadelphia  College  of  Pharmacy,  De- 
cember 8,  1913. 


62  Standardisation  of  Heart  Tonics.  {^ebruar'y,^™' 

mingham  physician  by  the  name  of  Withering,1  published  in  1785  the 
first  reliable  observations  of  the  medicinal  properties  of  this  drug. 
The  diuretic  properties  of  Digitalis  were  first  observed,  but  after 
the  middle  of  the  last  century  its  ability  to<  slow  the  heart  so  impressed 
the  medical  profession  that  Digitalis  was,  and  is  even  to  this  day, 
often  used  indiscriminately  for  all  conditions  where  the  heart  beat 
is  irregular  or  rapid.  It  can  now  be  demonstrated  that  Digitalis  is 
only  of  particular  value  in  a  very  limited  number  of  diseases  of  the 
heart  and  mainly  in  auricular  fibrillation. 

So  far  as  showing  the  rate  of  the  heart  beats  is  concerned,  it  may 
be  laid  down  as  a  law,  that  Digitalis  is  far  less  effective  when  the 
rhythm  of  the  heart  is  normal  than  when  there  is  auricular  fibrillation.2 
Most  authors  state  that  digitalis  causes  constriction  of  the  blood- 
vessels and  consequently  a  rise  in  blood-pressure,  yet  I  have  not  been 
able  to  demonstrate  more  than  slight  variations  in  blood-pressure  in 
test  animals,  although  various  lots  of  tinctures,  fluid  extracts  and 
proprietary  preparations  have  been  tried. 

Mackenzie  3  has  made  numerous  observations  on  various  classes 
of  patients  and  refutes  the  idea  that  the  administration  of  Digitalis 
has  a  tendency  to  produce  fatal  syncope,  provided  the  drug  is  stopped 
as  soon  as  nausea  and  vomiting  appear  or  when  the  heart  rate  falls 
below  50  per  minute. 

When  the  rhythm  of  the  heart  is  normal  the  first  symptom  is  loss 
of  appetite,  if  drug  is  continued,  vomiting,  feeling  of  malaise,  head- 
ache, and  very  little  diarrhoea  may  be  reported. 

Famulener  and  Lyons  5  state  that  the  digitalis  glucosides  act  not 
only  on  the  heart  but  directly  on  the  central  nervous  system,  first 
stimulating  then  depressing  it.  Cushny  6  states  that  "  the  chief  thera- 
peutic use  is  to  counteract  certain  changes  in  the  circulation,  which 
result  in  the  blood  accumulating  in  the  veins  in  too  large  quantities 
while  the  arteries  are  less  filled  than  usual.  In  cases  of  dilation  of 
the  heart  with  a  weak  and  insufficient  systole,  its  action  is  almost 
specific. 

"  In  these  cases  the  action  is  very  simple — the  increased  ventricu- 
lar systole  approaches  the  normal,  the  output  of  the  heart  is  increased, 
and  in  some  cases  the  dilation  is  diminished  by  the  direct  action  of 
the  drug.  The  effect  is  an  increased  velocity  and  pressure  in  the 
arteries  and  improved  nutrition  of  the  whole  body." 

There  is  no  doubt  that  Digitalis  relieves  distress  and  dropsy  and 
has  been  directly  responsible  for  numerous  cures,  yet  it  is  possible 


AFebraairy  ^iuET' }     Standardization  of  Heart  Tonics.  63 

that  these  favorable  results  may  be  attributed  to  some  other  reason 
than  its  effect  on  the  heart,  per  se. 

It  is  needless  to  say  that  Digitalis  has  been  given  thousands  of 
times  when  its  use  was  not  indicated  and  doubtless  its  failure  to  pro- 
duce favorable  results  under  improper  conditions  has  been  responsible, 
more  than  once,  for  condemnation  of  the  particular  preparation  of 
digitalis  being  used.4  It  has  been  repeatedly  stated  that  analogous 
preparations  of  digitalis  made  by  various  manufacturers  differ  mark- 
edly in  strength,  that  digitalis  preparations  rapidly  deteriorate  and 
that  only  the  leaves  of  the  first  year's  plant  are  active.  It  is  no  doubt 
true  that  analogous  digitalis  preparations  differ  markedly  in  strength,7 
but  it  is  very  doubtful  if  the  usual  galenical  preparations  deteriorate 
rapidly,8  or  that  only  the  leaves  of  the  first  year's  plant  are  active.9 

It  is  possible,  but  not  at  all  probable,  that  only  the  digitalis  plants 
which  are  in  flower  are  physiologically  active  and  this  need  not  ex- 
clude the  first  year's  plants  as  John  A.  Bornemann  10  has  shown  me 
a  digitalis  plant  with  plenty  of  flowers  on  it,  although  it  was  a  plant 
of  the  first  year's  growth.  Certain  it  is  that  the  therapeutic  action 
of  digitalis  as  stated  by  various  authors  is  sadly  confusing  and  no 
doubt  much  of  this  confusion  is  due  not  alone  to  clinical  reports  where 
digitalis  was  not  indicated,  but  to  the  pharmacologic  variability  of  the 
preparations  themselves. 

Chemistry  of  Digitalis. 

Almost  every  pharmaceutical  chemist  of  note  has  tried  to  isolate, 
unchanged,  the  complex  active  principles  that  are  present  in  digitalis. 
The  great  Schmiedeberg  and  Kiliani  agreed  that  the  four  glucosides 
which  they  separated  and  called  digitoxin,  digitalin,  digitalein  and 
digitophyllin,  possess  a  true  digitalis  action.  They  separated,  in  addi- 
tion, other  glucosides  such  as  digitonin,  digitin  and  digitoflavin,  but 
they  considered  these  decomposition  products.  Several  carbohy- 
drates which  came  from  the  decomposition  of  the  glucosides,  were 
also  described. 

When  one  looks  up  the  vast  literature  on  the  chemistry  of  digitalis 
it  is  quite  evident  that  different  glucosides  are  sometimes  given  the 
same  name  by  different  authors  and  vice  versa. 

Recently  Kraft 11  has  contributed  an  admirable  article  on  this 
subject  and  his  work  is  now  generally  accepted.  He  claims  that  both 
Schmiedeberg  and  Kiliani  worked  with  German  digatalin,  a  commer- 
cial product  made  largely  from  digitalis  seeds,  hence  their  results  are 


64  Standardisation  of  Heart  Tonics.  {A^u°^^a- 

not  reliable  for  digitalis  leaves.  Kraft  has  isolated  a  new  active 
glucoside  which  he  calls  Gitalin,  which  probably  has  the  chemical 
formula  C28H48O10.  This  glucoside  is  amorphous  but  forms  a 
crystalline  hydrate,  C28H48O104H2O.  Gitalin  readily  decomposes  in 
any  solvent  except  chloroform  into  anhydrogitalin  C23H4609  which  on 
hydrolysis,  with  a  dilute  acid  in  the  presence  of  alcohol,  changes  to 
anhydrogitaligenin  C22H3405  and  a  sugar  which  was  found  to  be 
identical  with  Kiliani's  digitoxose.  Another  new  glucoside  was  also 
isolated.  This  he  called  Gitin,  and  it  is  inactive  physiologically.  It 
is  crystalline  and  melts  at  265  °  C.  It  is  considered  similar  to,  but  not 
identical  with,  Kiliani's  digitonin. 

Digitoxin  is  often  considered  the  chief  active  glucoside  in  digitalis 
and  chemical  determinations  of  this  constituent  have  been  frequently 
made  in  the  hope  of  finding  a  relationship  between  the  digitoxin  con- 
tent and  the  therapeutic  activity,  but  the  results  in  almost  every  case 
have  proved  a  failure.12  If  the  digitoxin  from  a  given  amount  of 
drug  is  isolated  it  will  be  found  that  the  total  amount  of  digitoxin  is 
very  much  less  toxic  than  the  amount  of  drug  from  which  it  was 
obtained,  hence  it  seems  absolutely  necessary  to  resort  to  pharmaco- 
logical standardization  if  any  definite  idea  of  the  therapeutic  strength 
is  desired. 

Pharmacologic  Standardization  of  Digitalis. 
At  least  three  distinctly  different  pharmacologic  methods  have 
been  proposed  for  the  standardization  of  Digitalis — the  frog  method, 
the  guinea  pig  method,  and  the  cat  method. 


The  Frog  Method. 
The  frog  method  was  first  proposed  by  Houghton  in  1898. 13  He 
found  that  "  fairly  accurate  data  could  be  obtained  from  the  appli- 
cation of  a  solution  containing  Strophanthin,  Digitalin,  etc.,  to  the 
laid-bare  frog's  heart,  by  comparing  the  action  of  the  drug  thus 
tested  with  that  of  a  sample  of  known  strength."  After  much  ex- 
perimental work  this  method  was  replaced  by  the  use  of  a  simpler 
one — namely,  the  determination  of  the  minimum  lethal  dose  for  frogs 
under  definite  conditions.  Although  the  original  method  as  modified 
by  Houghton  gives  quite  satisfactory  results,  yet  various  workers 
have  proposed  certain  changes  in  the  conditions  under  which  the  test 
is  to  be  made.  For  example,  twelve  hours  was  specified  as  being  the 
length  of  time  that  observations  should  be  made  after  injection  of  the 


AFe'braa^y  *m£' }     Standardisation  of  Heart  Tonics.  65 

frogs.  As  this  is  usually  inconvenient,  these  observations  were 
made  after  one  hour,  two  hours,  six  hours,  or  twenty-four  hours. 
Some  workers  began  to  pith  the  frog  at  the  end  of  one  hour  and 
make  a  direct  examination  of  the  condition  of  the  heart,  for  it  was 
found  that  sometimes  frogs  would  be  apparently  normal  yet  their 
hearts  had  been  stopped  by  the  drug. 

Dr.  Hale  14  observed  that  more  concordant  results  were  obtained 
when  the  frogs  were  kept  at  the  uniform  temperature  of  22 0  C.  It 
would  neither  be  interesting  nor  instructive  to  relate  the  various  modi- 
fications that  have  been  proposed  for  the  Houghton  method. 

Edmunds  and  Hale,15  Edmunds  and  Cushny,16  and  Focke  17  have 
specified  various  conditions  under  which  the  "  frog  test "  is  to  be 
made,  but  none  of  these  methods  make  any  provision  to1  standardise 
the  frogs  that  are  used. 

It  is  known  that  variety,  weight,  sex,  season,  and  temperature 
affect  the  resistance  of  frogs  and  hence  it  is  possible  to>  obtain  different 
results  with  different  lots  of  frogs.  In  order  to  eliminate  these  factors 
of  unknown  significance  in  any  particular  case,  Houghton  and 
Hamilton  have  suggested  that  a  standard  be  used  in  testing  the 
resistance  of  every  lot  of  frogs,  at  the  time  the  test  is  made.  Upon 
these  data  "  The  Heart  Tonic  Unit  " 18  is  computed  in  every  case. 

The  standard  they  propose  to  use  is  crystalline  Strophanthin 
which  is  prepared  from  an  authentic  specimen  of  the  official  drug, 
Strophanthus  Komibe,  and  has  been  studied  in  detail  by  Braun  and 
Closson.19  The  outline  of  the  present  method  as  modified  by  Hough- 
ton is  as  follows : 

Frogs  should  all  be  of  same  species,  a  convenient  variety  is  the 
Rana  Pipiens.  They  should  all  be  of  weights  between  15  and  35  gm. 
and  the  weights  should  not  vary  more  than  25  per  cent,  in  any  one 
assay.  Before  being  used  the  frogs  may  be  kept  in  any  convenient 
place  where  the  water  can  be  frequently  changed  and  kept  at  a  tem- 
perature of  about  220  C.  During  the  test  the  frogs  can  advan- 
tageously be  kept  in  wire  cages  with  sheet  iron  bottoms,  standing 
in  trays  of  running  water,  but  the  depth  of  water  in  the  cages  should 
not  exceed  one-half  an  inch.  Scales  for  weighing  the  frogs  should  be 
accurate  within  0.5  gm.  The  necessary  apparatus  consists  of  volu- 
metric flasks,  cylinders,  graduated  pipettes  and  a  1  c.c.  pipette 
graduated  in  hundredths  of  a  cubic  centimetre  and  fitted  with  a  hypo- 
dermic needle  or  drawn  out  into  a  fine  point  for  injecting. 


66  Standardisation  of  Heart  Tonics.      { February  Pi9i™' 

The  solution  to  be  injected  should  not  contain  more  than  10  per 
cent,  alcohol  and  the  dilution  should  be  made  with  physiological  salt 
solution  (0.85  per  cent.  NaCl). 

The  doses  are  calculated  on  the  weight  of  the  frog,  i.e.,  the 
M.  L.  D.  is  the  minimum  lethal  dose,  per  gram  weight  of  frog. 
For  example,  when  the  frogs  are  of  average  resistance  the  M.  L.  D. 
of  Strophanthin  is  0.000,001  gm.  per  gram  weight  of  frog,  i.e.,  for  a 
30  gram  frog  the  lethal  dose  of  Strophanthin  is  .000,03  gm->  which 
should  be  so  diluted  that  this  amount  is  contained  in  approximately 
0.5  c.c.  Several  series  of  tests  are  necessary  to  establish  the  activity 
of  any  sample  of  unknown  strength  and  since  the  frogs  vary  in 
resistance  among  themselves  and  also  because  of  conditions  more  or 
less  beyond  control,  the  standard  Strophanthin  must  be  tested  at  the 
same  time.  When  the  M.  L.  D.  of  sample  and  of  standard  are 
obtained  the  activity  can  readily  be  expressed  in  Heart  Tonic  Units 
(H.  T.  U.)  by  reference  to  a  table. 

In  the  method  just  given  the  observations  are  to  be  made  at  the 
end  of  twenty-four  hours,  hence  the  one-hour  method  has  certain 
advantages  when  several  series  are  desired  on  a  single  sample  as  soon 
as  possible.  When  the  one-hour  method  is  used  it  is  necessary  to  not 
consider  all  frogs  that  have  not  absorbed  the  dose  injected. 

The  One-Hour  Method. 

"  In  this  method  the  frogs  are  secured  and  kept  in  the  manner 
already  described,  weighed,  and  such  a  dose  is  injected  that  the 
heart  will  be  found  in  complete  systolic  contraction  at  the  end  of 
exactly  sixty  minutes.  The  drug,  properly  diluted  so  as  to  make 
a  volume  of  0.5  to  1  c.c,  is  injected  into  the  anterior  lymph  sac  by 
means  of  a  glass  pipette.  Shortly  before  the  hour  is  up  the  frog  is 
pithed,  tied  to  a  frog  board,  and  the  heart  is  exposed  in  the  usual 
manner.  If  the  heart  is  still  beating,  the  dose  has  been  too  small 
and  must  be  increased  in  subsequent  trials.  In  the  first  series  doses 
are  chosen  with  wide  limits,  which  in  a  second  and  third  series  of 
animals  are  narrowed  down  until  the  smallest  amount  of  the  drug 
which  will  produce  systolic  standstill  in  one  hour  is  found.  Usually 
three  series  of  frogs  are  sufficient  to  assay  one  preparation,  but  in 
case  of  any  irregularity  in  the  reaction  of  any  of  the  frogs  a  fourth 
or  even  a  fifth  series  may  be  necessary." 

The  method  of  Focke  17  is  long  and  complicated  and  does  not 
appear  to  have  any  advantage  over  the  other  frog  methods  that  have 
been  described. 


Am.  Jour.  Pharm.  ) 
February,  1914.  j 


Standardisation  of  Heart  Tonics. 


67 


Guinea  Pig  Method. 

Reed  and  Vanderkleed  20  first  advocated  the  advantages  of  using 
the  guinea  pig  as  the  test  animal  although  Houghton  13  had  pre- 
viously tried  pigs  but  considered  the  frog  test  more  reliable. 

The  closer  biologic  relation  of  the  guinea  pig  to  man  appears  to 
be  one  important  reason  for  preferring  guinea  pigs.  It  is  claimed  21 
that  "  frogs  not  only  show  the  pharmacological  action  of  the  drug 
under  test,  but  they  react  with  so  near  an  approach  to  uniformity  that 
the  medicinal  value  of  a  tested  specimen  can  be  gauged  by  the  deter- 
mination of  the  minimum  fatal  dose — for  the  slowing  of  the  heart 
beat  and  the  systolic  emphasis  produced  by  active  heart  tonics  are 
directly  proportioned  to  the  quantity  of  the  drug  administered,  and 
under  progressive  doses  at  last  reach  a  point  which  is  incompatible 
with  life." 

Details  of  Reed  and  Vanderkleed  Method  for  Testing  Digitalis 
and  its  Preparations. 

If  Digitalis  leaves  are  to  be  tested  a  tincture  is  first  prepared 
from  the  sample  by  the  U.  S.  P.  process. 

An  amount  of  any  alcoholic  preparation  representing  one-tenth 
of  a  gramme  of  Digitalis  Leaves  is  placed  in  a  very  small  watch  glass 
and  the  excess  of  alcohol  evaporated  from  it  at  room  temperature 
by  placing  the  vessel  in  a  current  of  air.  This  residue  is  then  care- 
fully washed  into  a  Hitchen's  syringe  22  with  sufficient  physiologi- 
cal salt  solution  to  make  the  total  volume  two  cubic  centimetres. 

The  hypodermatic  needle  is  previously  sealed  with  sufficient  petro- 
latum to  prevent  loss  of  this  solution. 

Two  cubic  centimetres  of  physiological  salt  solution  is  placed  in 
the  side-arm  of  the  syringe  and  the  needle  inserted  under  the  skin 
of  a  guinea  pig  weighing  about  250  gm. 

The  solution  of  the  drug  is  then  injected  and  the  last  portions 
washed  under  the  skin  with  the  physiological  salt  solution  which  was 
placed  in  the  side  arm,  without  removing  the  needle. 

Great  precaution  is  taken  to  inject  accurate  amounts  and  always 
a  total  of  four  cubic  centimetres  of  liquid  (2  c.c.  of  solution  of  drug 
and  2  c.c.  of  physiological  salt). 

After  the  injection,  the  guinea  pig  is  kept  under  close  obser- 
vation and  evidences  and  time  of  salivation,  purgation  and  convul- 
sions noted.  If  the  pig  should  not  develop  these  symptoms  and  die 
within  two  hours,  another  pig  is  injected  with  a  larger  quantity  of 
the  drug. 


68  Standardisation  of  Heart  Tonics.  {^Zy^oit 

The  tests  are  repeated  until  the  amount  of  the  drug  is  found 
which  will  produce  the  characteristic  symptoms  of  Digitalis  poisoning 
and  kill  a  250  gm.  guinea  pig  in  two  hours. 

Post-mortem  examinations  are  always  made  to  note  the  con- 
dition of  the  heart  and  dilation  of  the  blood-vessels. 

In  testing  solid  preparations  of  Digitalis  a  weighed  quantity  of 
the  preparation  is  shaken  with  a  definite  amount  of  physiological 
salt  solution  so  that  two>  cubic  centimetres  of  the  liquid  will  represent 
one-tenth  gramme  of  the  drug.  This  method  has  been  found  quite 
satisfactory,  but  Pittinger  23  has  found  that  more  concordant  results 
are  obtained  if  the  time  of  observation  is  extended  from  two  hours 
to  twenty-four  hours.  One  disadvantage  to  the  method  is  that  the 
cost  of  the  required  pigs  is  usually  greater  than  the  frogs  necessary 
for  Houghton's  method.  This  objection  is  largely  overcome  by  manu- 
facturers of  antitoxin  who  can  use  the  pigs  that  have  survived  the 
antitoxin  tests  for  digitalis  tests.  These  pigs  cannot  again  be  used 
for  testing  serum  on  account  of  anaphylaxis,  and  by  the  time  they 
have  completely  recovered  from  the  antitoxin  tests  they  may  weigh 
much  more  than  250  gm.,  which  is  the  weight  specified.  No  pro- 
vision is  made  for  the  varying  susceptibility  of  the  pigs  and  it  is 
doubtful  if  the  pig  test,  as  it  is  usually  carried  out,  will  give  any  more 
reliable  results  than  a  larger  number  of  frogs  that  have  been  "  stand- 
ardized "  with  crystalline  strophanthin. 

The  Cat  Method  of  Hatcher  and  Brodie.24 

This  method  is  based  upon  the  determination  of  the  minimum 
lethal  dose  for  cats.  The  cat  is  anaesthetized  with  ether  and  about 
one-half  of  the  amount  of  the  preparation  being  tested  necessary  to 
kill  the  animal  is  injected  directly  into  the  venous  circulation.  The 
originators  of  this  test  have  found  that  if  preparations  of  digitalis  or 
other  members  of  this  series  are  injected  until  the  cat  dies,  the  results 
will  usually  be  too  high,  hence,  after  twenty  minutes  a  1  to  100,000 
solution  of  Merck's  Ouabain  is  cautiously  injected  until  the  cat  shows 
signs  of  dying,  namely,  rapid  respiration,  which  soon  becomes  irregu- 
lar and  is  accompanied  by  convulsive  movements.  The  Ouabain 
should  be  injected  in  such  amounts  that  the  cat  should  die  ninety 
minutes  after  the  beginning  of  the  test. 

The  "  cat  unit "  is  the  amount  of  crystalline  Merck's  Ouabain 
which  is  fatal  within  about  ninety  minutes  to  each  kilogram  body 


Ve'braary,Pih9air4m'}     Standardization  of  Heart  Tonics.  69 

weight  of  the  cat.  This  amounts  to  0.1  milligramme  of  the  Ouabain 
and  the  number  of  "  cat  units  "  in  one  cubic  centimetre  of  the  prep- 
aration being  tested  is  computed  from  the  data  obtained.  Eckler  25 
has  reported  serious  disadvantages  to  this  method,  and  it  is  doubtful 
if  it  will  ever  have  the  popular  favor  the  other  two  methods  enjoy. 

Factors  Relating  to  the  Standardization  of  Digitalis. 

It  may  easily  be  seen  that  the  last  word  has  not  been  said  in 
regard  to  the  standardization  of  Digitalis  and  this  unsettled  condition, 
in  its  standardization,  is  certain  to  prevail  until  the  therapeutic  uses 
and  chemistry  of  the  drug  are  agreed  upon. 

It  is  true  that  some  fault  can  be  found  with  the  methods  we  have 
outlined  and  no  doubt  many  factors  will  soon  be  eliminated. 

At  the  present  time,  it  is  possible  to  determine  by  physiological 
tests  with  reasonable  accuracy  the  variability  of  the  crude  drug,  the 
stability  of  its  preparations,  and  to  prepare  preparations  of  con- 
siderable uniformity.26 

Other  Heart  Tonics. 

What  has  been  said  in  regard  to  the  methods  used  for  standard- 
izing Digitalis  applies  also  to  preparations  of  Strophanthus,  Squill  and 
Convallaria.  Strophanthus  seems  to  be  more  certain  in  its  action 
than  digitalis  and  can  also  be  advantageously  tested  by  the  blood- 
pressure  method  upon  dogs. 

Cactus  grandiHorus  has  long  been  used  empirically  with  appa- 
rently favorable  results,  yet  competent  pharmacologists  have  reported 
that  it  has  no  action  analogous  to  digitalis 27'28.  Graeber 29  has 
recently  reported  the  presence  of  both  alkaloids  and  glucosides  in 
this  drug  and  publishes  experiments  on  frogs  which  "  indicate  that 
Cactus  grandiflorus  actually  is  possessed  of  an  action  upon  the  heart 
such  as  belongs  to  the  substances  of  the  digitalis  group."  In  all  his 
frog  experiments  the  frequency  of  the  pulse  was  reduced  and  the 
systole  strengthened. 

Sparteine  sulphate  is  considered  a  drug  of  mediocre  importance 
as  a  "  heart  tonic,"  yet  Pettey  30  considers  that  Sparteine  is  unappre- 
ciated because  it  is  not  given  in  sufficient  doses.  He  recommends  the 
use  of  2  grain  doses  as  a  true  and  reliable  heart  tonic,  an  excellent 
non-irritating  diuretic  and  states  that  this  dose  is  entirely  free  from 
untoward  or  objectionable  effects. 


70  Standardisation  of  Heart  Tonics.  {A?eb™?S,Pi»i™' 

Work  of  the  Normal  Heart. 
Few  realize  the  vast  amount  of  work  performed  each  day  by  the 
heart  of  the  normal  adult.   One-fifth  the  total  muscular  energy  of  the 
body  is  used  in  propelling  the  heart  and  about  twelve  tons  of  blood 
are  pumped  each  day. 

New  Methods  of  Observing  Conditions  of  the  Heart. 
The  electro-cardiographic  method  31  has  made  possible  not  only 
the  accurate  diagnosis  of  diseases  of  the  heart  but  also  enables  the 
physician  to  observe  the  effects  of  the  medicine  he  has  prescribed. 
The  practice  of  medicine  under  these  conditions  has  become  scientific, 
not  empiric,  and  if  uniform  preparations  of  the  "  heart  tonics  "  can 
be  supplied,  the  physician  needs  only  to  consider  the  idiosyncrasy  of 
the  patient. 

Summary. 

In  presenting  this  subject  I  have  attempted  to  dwell  not  alone  on 
the  methods  used  in  standardizing  the  "  heart  tonics  "  but  the  various 
factors  that  must  be  considered  in  producing  reliable  and  potent  prep- 
arations. The  clinical  side  of  the  problem  must  not  be  lost  sight  of, 
and  when  a  preparation  is  made  that  will  produce  certain  therapeutic 
results  it  is  of  vital  importance  to  produce  another  lot  having  the 
same  action.  Uniformity  is  practically  as  important  as  potency. 
When  a  competent  observer  like  Faught 32  says  "  Usual  preparations 
are  variable  and  cannot  be  depended  upon  unless  coming  from  a 
reliable  source.  I  have  seen  less  effect  follow  the  administration 
of  20  minims  of  a  poor  preparation  than  5  minims  of  a  good  active 
one  "  it  is  time  to  improve  conditions.  Conditions  can  be  improved 
by  the  adoption  of  pharmacological  standards  and  methods  for  these 
drugs.  At  the  present  time  the  manufacturers  who  have  wisely 
adopted  physiological  standardization  of  their  products  often  have 
different  standards  while  those  that  have  not  adopted  physiological 
standards  have  no  assurity  that  these  important  drugs  are  even  active. 

-  BIBLIOGRAPHY. 

1  Withering,  "  An  Account  of  the  Foxglove  and  Some  of  its  Medicinal  Uses." 

2  Mackenzie,  "  Digitalis  "  Heart,  volume  2,  No.  4,  page  279. 

3  Mackenzie,  "  A  Scheme  for  Investigating  the  Treatment  on  the  Human 

Heart "  Heart,  volume  2,  page  9. 
*  Berkeley,  Merck's  Archives,  September,  1910,  page  275. 

5  Proceedings  of  American  Pharmaceutical  Association,  1902,  page  415. 

6  Cushny,  "  Pharmacology  and  Therapeutics." 


Am.  Jour.  Pharm.  ) 
February,  1914.  j 


Colloids  and  Crystals. 


71 


T  Journal  of  Amer.  Med.  Assoc.,  September  13,  1913. 

8 "  Observations  on  the  Keeping  Properties  of  Digitalis  and  Some  of  Its  Prep- 
arations," Hatcher  and  Eggleston.  American  Journal  of  Pharmacy, 
1913,  page  203. 

9  Miller  and  Baker,  8th  International  Congress  of  Applied  Chemistry. 

10  Personal  Communication. 

11  Kraft,  Arch,  der  Pharm.,  1912. 

V£  Edmunds  and  Hale,  "  The  Physiological  Standardization  of  Digitalis." 
18  Houghton,  Journal  of  American  Medical  Association,  June  7-10,  1898. 
"Hale,  The  Physiological  Standardization  of  Drugs,  American  Journal  of 
Pharmacy,  191 1. 

16  United  States  Hygienic  Laboratory,  Bulletin  48. 

18 "  Laboratory  Guide  in  Experimental  Pharmacology,"  Geo.  Wahr,  publisher. 

17  Focke,  Arch.  d.  Pharm.,  1903,  241,  page  678. 

18  Hamilton,  "  The  Heart  Tonic  Unit,"  American  Journal  of  Pharmacy,  1912, 

page  97. 

19  Braun  and  Closson,  "  The  Chemical  Constitution  of  Crystalline  Strophan- 

thus,"  Jour,  of  Amer.  Pharm.  Assoc.,  1913. 

20  Reed  and  Vanderkled,  American  Journal  of  Pharmacy,  1908,  page  no. 

21  "  Standardization  of  Pharmaceutical  and  Biological  Products,"  Parke,  Davis 

and  Co. 

22  Hitchens.    Journal  of  Experimental  Medicine,  1905. 

23  Pittinger,  1912  Proceedings  American  Therapeutic  Society. 

34  Hatcher  and  Brodie,  American  Journal  of  Pharmacy,  1910,  page  362. 

25  Eckler,  American  Journal  of  Pharmacy,  October,  191 1. 

26  Hale,  Factors  Relating  to  the  Standardization  of  Digitalis ;  Proceedings  of 

American  Pharmaceutical  Association,  1909. 

27  Hatcher  and  Bailey,  Jour.  Amer.  Med.  Assoc.,  1907,  page  1021. 

28  Lyon  and  Quail,  Jour.  Amer.  Med.  Assoc.,  1910,  pages  455,  459,  508. 
19  Graeber,  Therapeutische  Monatshefte,  1913,  page  581. 

30  Pettey,  "  The  Therapeutic  Virtues  of  Sparetine  Sulphate."    Clinical  Medi- 

cine, Sept.,  1913. 

31  Lewis,  "  Clinical  Electrocardiography." 

52  Faught,  "  Blood-Pressure  from  Clinical  Standpoint,"  page  268. 

COLLOIDS  AND  CRYSTALS,  THE  TWO  WORLDS  OF 

MATTER* 

By  Robert  H.  Bradbury, 
Head  of  the  Department  of  Science  in  the  Southern  High  School,  Philadelphia. 

When  a  solid  is  brought  into  contact  with  a  liquid  the  result 
depends  upon  the  nature  of  both.    There  may  be  apparently  an  entire 

*  Presented  at  the  meeting  of  the  Section  of  Physics  and  Chemistry  held 
Thursday,  April  10,  1913,  and  reprinted  from  Jour.  Franklin  Institute,  Sep- 
tember, 191 3. 


72 


Colloids  and  Crystals. 


j  Am.  Jour.  Pharm. 
(   February,  1914. 


absence  of  interaction,  as  when  rosin  is  shaken  up  with  water  or  chalk 
with  alcohol.  Or,  as  when  sugar  is  agitated  with  water,  the  solid 
may  disappear,  entering  into  solution  in  the  liquid.  The  study  of 
sugar  solution  shows  quite  clearly  that  the  connection  of  the  sugar 
molecules  with  each  other  has  been  completely  destroyed.  They  are 
dispersed  through  the  water  very  much  as  the  molecules  of  a  gas 
distribute  themselves  uniformly  in  a  vacant  space,  and  in  both  cases 
the  permanence  of  the  uniform  dispersion  is  due  to  the  incessant 
motion  of  the  molecules.  Were  the  molecules  at  rest,  both  the  sugar 
and  the  gas  would  settle  and  form  a  layer  on  the  bottom  of  the 
containing  vessel. 

However,  the  molecules  of  the  sugar  retain  their  structure  intact, 
the  action  being  limited  to  their  dispersion.  When  salt,  on  the  other 
hand,  is  dissolved  in  water,  a  further  breakdown  occurs,  the  molecule 
is  separated  and  ions  of  sodium  and  of  chlorine  move  about  in  the 
liquid.  Both  solutions  freeze  below  o°  C.  and  boil  above  ioo°  C. 
The  most  important  difference  between  them  is  that  the  salt  solution 
conducts  the  electric  current,  while  the  sugar  solution  is  as  poor 
a  conductor  as  water  itself. 

A  fourth  possibility  presents  itself  when  glue  or  gelatin  is  treated 
with  water.  The  gelatin  absorbs  water,  swells  up  and,  under  the 
influence  of  heat,  dissolves,  but  the  liquid  freezes  and  boils  at  prac- 
tically the  same  temperatures  as  pure  water.  The  study  of  the  solu- 
tion shows  that  the  dispersion  is  not  molecular.  The  particles  of 
gelatin  in  it  are  composed  of  variable  and  rather  large  numbers  of 
molecules.  A  system  like  this  gelatin  solution  which  presents  a  case 
of  very  fine  but  not  molecular  subdivision  is  called  a  colloidal  solution. 
There  are  certain  solids  such  as  gelatin  and  dextrin  (with  water), 
and  rubber  (with  benzene  and  carbon  disulphide),  which,  when  they 
dissolve  in  liquids,  are  invariably  dispersed  in  this  way.  Such  solids 
may  properly  be  referred  to  as  colloids.  They  are  all  amorphous. 
Crystallized  substances  never  yield  colloidal  solutions  by  mere  spon- 
taneous solution  in  a  liquid.  They  always  produce  molecular  or 
ionic  dispersions.  However,  the  phenomenon  of  colloidal  solution  is 
perfectly  general,  and  crystallized  substances  can  also  be  obtained 
in  this  condition,  but  not  by  mere  solution. 

It  is  an  interesting  fact  that  a  substance  which  yields  a  colloidal 
solution  with  one  solvent  may  form  an  ordinary  molecular  solution 
with  another.    Soap  is  an  example.    Its  concentrated  solution  in 


Am.  Jour.  Pharm.  ) 
February,  1914.  J 


Colloids  and  Crystals. 


73 


water  boils  at  about  ioo°,  freezes  at  about  o°,  and  exhibits  the  be- 
havior of  a  colloidal  solution  in  general.  On  the  contrary,  a  soap 
solution  in  alcohol  shows  the  normal  change  in  freezing  and  boiling 
points  corresponding  to  the  molecular  weight,  and  conducts  itself  in 
all  respects  like  an  ordinary  molecular  dispersion. 

II. 

Every  one  is  familiar  with  the  distinctions  between  solutions  and 
suspensions.  Suspensions  are  turbid  in  aspect,  and  the  solid  can  be 
removed  by  letting  it  settle,  or  by  nitration.  Solutions  are  clear,  dis- 
solved matter  does  not  subside  and  is  unaffected  by  filtering.  Col- 
loidal solutions  occupy  an  intermediate  position. 

Consider  for  a  moment  the  effect  of  increasing  subdivision  on 
a  suspension  of  finely-divided  gold  in  water.  So  long  as  the  diameter 
of  the  particles  is  much  greater  than  a  thousandth  of  a  millimetre,1 
the  system  will  be  turbid  and  the  gold  will  settle  rapidly.  But  the 
wave-length  of  visible  light  ranges  between  0.4  \x  and  0.7  /x,  and 
when  the  particles  become  smaller  than  this  they  can  no  longer  reflect 
light  and  the  liquid  will  appear  clear.  At  the  same  time  there  will 
be  a  rapid  falling  off  in  the  speed  of  settling.  Stokes  has  derived  a 
formula  for  the  velocity  of  subsidence,  V ,  of  small  spheres  of  radius 
R  and  density  ^  falling  in  a  liquid  of  density  S'  and  internal  friction  / 
under  the  force  of  gravity  g: 

Substituting  the  proper  values  for  gold  and  water  and  assuming 
a  radius  of  /x  for  the  particles,  the  value  for  V  is  about  14  centi- 
metres per  hour.  This  means,  of  course,  that  the  system  would  be 
a  coarse  suspension  and  would  clear  up  at  once.  But  when 
R  =  10  fx  fx,  V  is  only  about  a  centimetre  a  month.  This  begins 
already  to  be  fairly  permanent.  It  must  be  remembered  that  the 
high  density  of  gold  (19.5)  increases  the  rapidity  of  subsidence. 
If  we  make  the  calculation  for  S  =  3,  which  is  about  the  density 
of  arsenious  sulphide,  V  comes  out  only  about  a  millimetre  a  month. 


1  It  is  usual  to  employ  the  symbol  v>  (the  Greek  letter  mu)  for  the  thou- 
sandth of  a  millimetre.  In  the  same  way  ix  fx  indicates  the  millionth  of  a 
millimetre. 


74 


Colloids  and  Crystals. 


Am.  Jour.  Pharm. 
February,  1914. 


So  much  for  calculation.  Now  what  are  the  facts  ?  As  a  matter 
of  fact,  the  dispersed  substance  in  a  colloidal  solution  does  not  settle 
at  all,  so  long  as  the  subdivision  is  maintained.  Colloidal  gold  solu- 
tions have  been  preserved  unchanged  for  years.  I  have  a  solution 
of  arsenious  sulphide  which  has  remained  apparently  unchanged  for 
three  years  and  whose  countless  particles  can  readily  be  seen,  engaged 
in  their  incessant  Brownian  movement,  with  an  ordinary  oil  immer- 
sion lens.  Whenever  settling  does  occur,  it  is  preceded  by  the 
aggregation  of  the  particles  into'  larger  particles,  which  finally  attain 
a  diameter  of  fx  or  over,  and  slowly  subside. 

Here,  then,  is  an  apparent  discrepancy  between  Stokes'  law  and 
the  facts.  The  law  informs  us  that  the  speed  of  subsidence  decreases 
rapidly  with  decreasing  radius  of  the  particles,  but  it  does  not  lead 
us  to  expect  the  total  absence  of  settling  which  presents  itself  when 
the  average  radius  is  10  f-  /*  or  thereabout. 

The  explanation,  of  course,  is  molecular  motion,  or,  in  other 
words,  heat.  The  particles  are  battered,  on  all  sides,  by  a  hail-storm 
of  molecular  impacts.  If  the  particle  is  large,  the  blows  of  the  mole- 
cules of  the  solvent  in  different  directions  neutralize  each  other. 
But  when  the  particle  is  not  so  very  much  larger  than  the  molecules 
themselves  a  molecule  striking,  say  on  the  left,  will  give  the  particle 
a  very  perceptible  push  toward  the  right,  "just  as  a  cork  follows  better 
than  a  large  ship  the  motion  of  the  waves  of  the  sea."  2  As  the 
dimensions  of  the  particle  approach  the  molecular  dimensions  it 
begins  to  behave  like  a  molecule  and  is  swept  along  in  the  endless 
molecular  movement.  The  cause  which  prevents  the  particles  in  a 
colloidal  solution  from  settling  is  in  no  way  different  from  the  cause 
which  prevents  the  earth's  atmosphere  from  subsiding  to  a  snowy 
layer  a  few  feet  deep  on  the  surface  of  the  planet. 

It  is  worth  remembering,  also,  that  the  particles  of  the  dispersed 
phase  ordinarily  possess  an  electric  charge,  which  is  usually  negative. 
The  effect  of  the  repulsion  of  these  similar  charges  would  be  to*  pre- 
serve the  distribution  of  the  particles  throughout  the  liquid.  It  is  a 
fact  that,  when  the  charges  are  removed,  the  system  becomes  instable 
and  subsidence — preceded  by  coalescence  of  the  small  particles — 
readily,  but  not  necessarily,  occurs. 


2  Perrin. 


Am.  Jour.  Pharm.  ) 
February,  1914.  j 


Colloids  and  Crystals. 


75 


III. 

On  the  subject  of  the  classification  of  colloid  systems  we  must 
be  very  brief.  One  proposal  subdivides  them  into  suspensoids,  such  as 
the  sols  3  of  gold  and  arsenious  sulphide,  in  which  the  dispersed 
phase  is  solid,  and  emulsoids,  in  which  the  dispersed  phase  is  liquid. 
This  classification  would  appear  to  be  an  attempt  to  extend  the 
familiar  distinction  between  liquid  and  solid  to  a  domain  in  which 
that  distinction  has  little  if  any  meaning.  To  assert  that  a  thing  is 
solid  is  to  say  that  it  has  a  definite  shape,  which  it  retains  with  some 
persistence.  There  is  not  the  slightest  reason  to  think  that  the 
particles  in  a  gold  sol  are  solid.  It  is  usual  to  assume  that  they  are 
spherical,  but  this  is  done  merely  because  it  is  the  simplest  assumption 
to  make.  There  are  faint  indications  that  they  really  have  the  form 
of  leaflets  or  of  little  rods,  but  they  appear  in  the  ultra-microscope 
simply  as  brilliant  dancing  points,  and  in  reality  we  know  nothing 
whatever  about  their  shape.  In  connection  with  this  it  is  interesting 
to  recall  the  fact  that  the  formation  of  a  crystal  begins  with  the 
appearance  of  minute  liquid  spheres  (globulites)  ,4  which  pass 
through  several  stages  (margarites,  longulites,  etc.)  before  the  crys- 
tal is  formed.  It  seems  possible  that,  under  such  enormous  sub- 
division, cohesion  retires  into  the  background  and  surface  tension 
assumes  the  chief  role,  so  that  the  gold  particles  are  rather  to  be 
compared  to  minute  drops  than  to  little  crystals. 

Enough  has  been  said  to  make  clear  the  uncertainty  which  attaches 
to  the  attempt  to  classify  colloid  solutions  according  to  the  state  of 
aggregation  of  the  particles.  A  better  classification  is  into  reversible 
and  irreversible  colloids,  according  to  the  way  in  which  the  dissolved 
substance  behaves  when  separated  from  the  solution.  Thus,  when  a 
gelatin  solution  is  evaporated  until  it  "  sets  "  it  is  only  necessary 
to  warm  the  jelly  with  water  to  obtain  it  again  in  colloid  solution. 
Gelatin  is  a  typical  reversible  colloid.  But  when  the  gold  is  caused 
to  separate  from  a  gold  sol — which  can  easily  be  brought  about  by 
adding  any  electrolyte  to  the  sol — the  gold  will  not  again  enter  into 
colloidal  solution.    Shaking  or  warming  with  water  gives  a  mere 

3  Thomas  Graham  introduced  the  term  sol  as  an  abbreviation  for  colloidal 
solution. 

4  Fink,  "  PoggendorfFs  Annalen,"  vol.  46,  p.  258  (1839)  ;  Schmidt,  "  Liebig's 
Annalen  der  Chemie,"  vol.  53,  p.  171  (1845);  Frankenheim,  "  PoggendorfFs 
Annalen,"  vol.  in,  p.  i  (i860). 


76 


Colloids  and  Crystals. 


I  Am.  Jour.  Pharm. 
\   February,  1914. 


suspension,  which  settles  at  once.  Gold  is  an  irreversible  colloid. 
The  distinction  is  fundamental.  Many  organic  colloids  are  reversible, 
while  it  is  rather  the  habit  of  the  inorganic  colloids  to  behave  in  the 
irreversible  way. 

IV. 

In  order  to  prepare  a  sol  containing  an  irreversible  colloid  all 
that  is  necessary  is  to  reduce  the  solid  to  extreme  subdivision  in  a 
liquid  in  which  it  is  insoluble.  The  electric  arc  furnishes  a  rapid 
and  simple  method.5  Two  gold  wires  about  2  mm.  thick  are  con- 
nected with  a  220-volt  circuit  and  brought  together  under  distilled 
water.  A  no-volt  circuit  can  be  used,  but  more  patience  is  required. 
Sols  of  platinum,  silver,  copper,  and  other  metals  can  be  made  in  the 
same  way.  By  related  electrical  methods,  using  such  liquids  as  pen- 
tane  and  anhydrous  ether,  Svedberg  6  obtained  sols  of  all  five  of  the 
alkali  metals.  The  colors  of  the  sols  agreed  with  those  of  the  vapors 
of  the  corresponding  metals. 

Chemical  reduction  of  a  salt  of  a  metal  furnishes  another  method 
which  has  been  largely  employed  by  Zsigmondy  7  and  other  investi- 
gators. For  instance,  a  very  dilute  solution  of  auric  chloride  is  mixed 
with  such  reducing  agents  as  formaldehyde,  hydroxylamine  or  an 
ethereal  solution  of  phosphorus.  The  gold  sols  obtained  in  this  way 
are  usually  red  by  transmitted  light,  the  particles  being  bright  green 
and  very  much  smaller  than  in  the  sols  obtained  by  the  electrical 
method. 

By  various  chemical  methods,  which  lack  of  space  forbids  us  .to 
discuss,  sols  of  sulphides  (CdS,  As2S;!,  Sb2S3,  etc.)  and  oxides 
(Fe203,  A120;!)  can  be  obtained.  The  sol  of  aluminum  oxide  is  im- 
portant on  account  of  its  connection  with  dyeing  and  mordanting. 
The  formation  of  the  blood-red  sol  of  ferric  oxide  by  adding  a  con- 
centrated solution  of  ferric  chloride  to  about  50  volumes  of  boiling 
distilled  water  is  a  simple  and  beautiful  lecture  experiment. 

In  making  colloidal  solutions  of  salts,  the  essential  thing  is  to 
mix  dilute  solutions  of  the  precipitants,  using  a  liquid  in  which  the 


5  Bredig,  Zcitschrift  fur  angeivandte  Chemie,  1898,  p.  951.  For  a  full 
account  of  Bredig's  work  with  the  platinum  sol  see  Zcitschrift  fur  physikal- 
ischc  Chcmic,  vol.  31,  pp.  258-353  (1899). 

6  Bcrichtc  dcr  dcutschcn  chcmischen  Gcsellschaft,  vol.  38,  p.  3616  (1905). 

7  See  his  monograph,  "  Zur  Erkentniss  der  Kolloide  "  (Jena,  1905),  which 
has  been  translated  by  Jerome  Alexander. 


Am.  Jour.  Pharm.  ) 
February,  1914.  / 


Colloids  and  Crystals. 


77 


insolubility  of  the  product  is  as  complete  as  possible.  Thus,  in  mixing 
very  dilute  solutions  of  sodium  sulphate  and  barium  chloride,  a  crys- 
talline precipitate  is  usually  obtained.  The  reason  is  that  barium 
sulphate  possesses  a  very  slight  but  real  solubility  in  water.  Hence 
the  liquid  in  contact  with  the  particles  first  formed  contains  enough 
barium  sulphate  to  nourish  their  growth  and  allow  them  to  develop 
to  crystals.  If  alcohol  is  added  to  the  sulphate,  before  the  barium 
chloride  is  introduced,  the  solubility  of  the  barium  sulphate  is  greatly 
reduced,  and  it  is  obtained  in  colloidal  solution  without  difficulty. 

In  the  same  way,  if  we  mix  water  solutions  of  sodium  hydroxide 
and  of  hydrochloric  acid  we  obtain  merely  an  ordinary  solution  of 
common  salt.  But  if  salt  is  produced  by  a  reaction  between  organic 
compounds  in  a  liquid  in  which  the  sodium  chloride  is  insoluble,  then 
a  colloidal  solution  is  obtained.  For  instance,  when  chlor-acetic  ester 
interacts  with  sodio-malonic  ester  a  grayish  opalescent  sol  of  sodium 
chloride  in  ethenyl  tri-carboxylic  ester  results :  CHX1  COOC2H5  -f- 
CHNa(COOC2H5)2  =  CH2(COOC2B5)  —  CH(COOC2H,)2  + 
NaCl.  At  low  temperatures,  in  such  liquids  as  toluene  and  chloro- 
form, even  ice  has  been  obtained  in  colloidal  solution. 

V. 

The  most  striking  property  of  the  reversible  colloids  is  that  they 
are  able  to  communicate  their  reversibility  to  the  irreversible  ones. 
Thus,  if  a  trace  of  gelatin  is  added  to  a  gold  solution,  the  gold 
becomes  much  more  difficult  to  coagulate  by  electrolytes,  and  when 
coagulated  it  can  be  dispersed  again  by  merely  warming  with  water. 
This  curious  protective  action  is  exerted,  in  greatly  varying  degree, 
by  most  reversible  colloids.  Direct  study  of  the  phenomenon  with 
the  ultra-microscope  shows  that  the  view  frequently  expressed  that 
the  gelatin  envelops  or  forms  a  film  around  the  gold  particles  is 
incorrect.  What  actually  happens  seems  to  be  a  direct  combination 
between  gelatin  particles  and  gold  particles,  which  then  pass  through 
the  reversible  changes  together. 

Protective  colloids  enjoy  a  wide  practical  application.  In  the 
manufacture  of  photographic  films  the  gelatin  retards  the  crystalliza- 
tion of  the  silver  bromide.  Ink  often  contains  a  colloid  which  pre- 
vents the  pigment  from  settling.  The  lubricant  "  aqua  dag  "  put  in 
the  market  by  the  Acheson  Company  consists  of  finely-divided  arti- 
ficial graphite,  held  up  by  a  protective  colloid.    Clay  is  made  plastic 


78 


Colloids  and  Crystals. 


j  Am.  jour,  Pharth. 
\   February,  1914. 


for  the  potter  by  an  empirical  process  which  involves  the  action  of 
protective  colloids  derived  from  decaying  vegetable  matter.  The 
addition  of  gelatin  in  making  ice  cream  depends  upon  its  protective 
action  in  preventing  the  growth  of  ice  crystals,  which  would  make 
the  product  "  gritty."  Without  doubt  protective  action  plays  an 
important  role  in  the  cleansing  action  of  soap.  This  has  been 
made  clear  by  some  recent  experiments  of  Spring.8  Lampblack, 
freed  from  oil  by  long  washing  with  alcohol,  ether,  and  benzene, 
forms  a  rather  stable  suspension  in  water,  but  the  lampblack  is  de- 
tained by  a  paper  filter.  If  the  filter  is  now  reversed,  so  that  the 
blackened  surface  is  outward,  and  water  poured  through  it,  the  lamp- 
black is  not  removed,  but  a  dilute  soap  solution  removes  the  coating 
and  cleanses  the  filter  at  once.  Finally,  lampblack  suspended — or  col- 
loidally  dissolved — in  soap  solution,  passes  through  a  filter  unchanged. 
It  is  of  much  practical  interest  that  there  is  a  well-marked  optimum 
in  the  concentration  of  the  soap  required  to  protect  the  lampblack. 
A  one  per  cent,  soap  solution  is  the  most  efficient.  In  two  per  cent, 
soap  solution  lampblack  sinks  about  as  rapidly  as  in  pure  water. 

VI. 

We  have  already  considered  the  probable  actual  condition  of  the 
particles  in  a  colloidal  solution  and  have  concluded  that,  for  the 
present,  no  very  definite  information  is  obtainable  about  the  matter. 
We  must  now  return,  for  a  moment,  to  the  subject  in  order  to  allude 
to  the  thesis  so  brilliantly  advocated  by  van  Weimarn,  the  Russian 
investigator,  who  holds  that  the  particles  are  of  necessity  minute 
crystals  and  that  there  is,  in  fact,  no  such  thing  as  amorphous  matter. 
He  even  goes  so  far  as  to  state  that  substances  like  air  and  water 
are  in  a  "  dynamic  crypto-crystalline  condition,"  though  I  have  been 
unable  to  understand  what  he  means  by  this  statement. 

Briefly,  the  evidence  that  van  Weimarn  adduces  to  the  support 
of  his  hypothesis  is : 

(1)  That  colloid  particles  will  grow  to  crystals  if  provided  with 
the  proper  nourishment,  namely,  a  dilute  solution  of  the  same 
substance. 

(2)  That  colloid  particles  are  capable,  when  introduced  into 

8  Kolloid  Zeitschrift,  vol.  4,  p.  161  (1909);  Kolloid  Zeitschrift,  vol.  6, 
pp.  11,  109,  164  (1910). 


Am.  Jour.  Pharm. ) 
February,  1914.  J 


Colloids  and  Crystals. 


79 


a  supersaturated  solution  of  the  same  substance,  of  discharging  the 
supersaturation  and  inducing  the  formation  of  crystals. 

Those  who  desire  to  follow  this  matter  further  should  read 
van  Weimarn's  little  book,  "  Grundziige  der  Dispersoidchemie," 
after  which  they  will  find  themselves  very  much  interested,  but 
somewhat  unconvinced.  Let  me  hasten  to  add  that  I  have  not  the 
least  desire  to  undervalue  the  brilliant  experimental  work  of  the  Rus- 
sian chemist.  It  is,  in  fact,  precisely  by  the  conception  of  more 
or  less  daring  hypotheses,  and  the  working  out  of  their  consequences, 
that  our  science  achieves  its  endless  victory  over  the  nescience 
about  us. 

VII. 

We  have  seen  that  the  wave-lengths  of  the  visible  radiations  are 
comprised  between  0.4  /x  and  0.7  With  objects  much  smaller,  the 
ordinary  microscopic  method  ceases  to  be  applicable.  Using  ultra- 
violet radiation  for  illumination,  quartz  lenses  in  the  microscope,  and 
receiving  the  image  with  the  photographic  plate  instead  of  the  eye, 
it  is  possible  to  advance  a  step  further  in  the  domain  of  the  infini- 
tesimal, but  only  a  step,  and  there  are  obvious  objections  to  the 
proceeding.  Since  some  of  the  particles  in  colloidal  solutions  are 
only  0.006  ^  in  diameter,  we  can  never  hope  to  see  them  as  little 
bodies  subtending  a  visual  angle.  The  ultra-microscope — -the  power- 
ful instrument  of  investigation  to'  which  most  of  our  knowledge  of 
colloid  systems  is  due — renounces  this  idea  and  makes  the  particles 
visible  merely  as  glittering  points  on  a  black  background.  The  sol 
is  placed  in  a  small  rectangular  glass  trough  and  a  horizontal  beam 
of  arc  light  or  sunlight  focussed  in  it.  The  microscope  is  placed 
vertically  above  the  trough.  It  will  at  once  be  seen  that  there  are  two 
fundamental  things  about  the  instrument :  to<  provide  intense  illumina- 
tion, and  to  make  sure  that  no  light  enters  the  microscope  except  the 
rays  which  emanate  from  the  particles.  The  principle  is  simple,  but 
the  system  of  diaphragms  and  lenses  needed  to  secure  the  second 
object  makes  the  ultra-microscope  an  elaborate  and  expensive  instru- 
ment in  practice. 

Cotton  and  Mouton  9  achieve  the  same  end  in  a  different  way. 
The  illumination  (arc  or  sunlight)  is  thrown  up  from  below  by  a 
paraboloid  reflector  so  ground  that  all  rays,  except  those  diffracted 


Compt.  Rendus,  vol.  136,  p.  1657  (1903). 


So 


Colloids  and  Crystals. 


{Am.  Jour.  Pharm. 
February,  1914. 


by  the  particles,  are  totally  reflected  from  the  cover-glass  over  the  sol. 
This  instrument  is  simple,  easily  adjusted  and  cheap.  It  is  made 
commercially  by  the  firm  of  Zeiss.  It  would  seem  to  be  admirably 
adapted  to  school  purposes.  In  fact,  after  a  look  into  the  ultra- 
microscope,  the  study  of  the  molecular  topics  ceases  to  be  drudgery 
and  becomes  a  positive  intellectual  need. 

VIII. 

Even  a  brief  glance  at  the  subject  of  colloid  systems  must  at  least 
mention  the  classic  work  of  Perrin  10  on  the  distribution  of  the  par- 
ticles in  suspensions  of  gamboge  and  mastic.  He  succeeded,  by  an 
ingenious  and  simple  method,  in  preparing  emulsions  of  gamboge 
in  water  in  which  the  spherical  yellow  granules  were  all  of  the  same 
diameter.  If  we  consider  a  mass  of  such  a  liquid  in  a  tube,  it  is  clear 
that  the  granules,  if  at  rest,  would,  since  they  are  denser  than  water, 
all  fall  to  the  bottom.  The  fact  that  they  remain  suspended  is  due  to 
their  movement.  In  other  words,  the  state  of  things  is  the  same  as 
in  the  earth's  atmosphere,  and  just  as  the  molecules  are  more  crowded 
near  the  earth's  surface,  so  the  granules  of  gamboge  must  be  more 
numerous  near  the  bottom  of  the  liquid  than  in  the  upper  layers. 
Perrin  verified  this  prediction  by  direct  counting  of  the  granules 
under  the  microscope.  The  barometric  formula  which  describes  the 
progressive  rarefaction  of  air  with  increasing  height  also  describes 
the  distribution  of  the  granules  in  Perrin's  uniform  emulsions.  The 
only  difference  is  that,  while  the  aviator  must  ascend  six  kilometres 
in  order  to  reach  air  half  as  dense  as  at  sea  level,  the  same  effect  is 
produced,  in  Perrin's  emulsion,  by  an  ascent  of  o.i  millimetre. 

That  the  mean  energy  of  rotation  of  a  molecule  must  be  equal  to 
its  mean  energy  of  translation  is  one  of  the  chief  propositions  of  the 
kinetic  theory.  Perrin  has  proved  this  by  direct  measurement  of  the 
rotation  of  granules  under  the  microscope.  For  this  purpose,  large 
granules  (15  /x)  of  mastic  were  employed.  These  are  far  too  heavy 
to  remain  suspended  in  water,  so  a  solution  of  urea  was  used.  For- 
tunately, the  granules  contain  little  inclusions  which  make  it  possible 
to  measure  their  rotation. 


10  Annates  de  Chimie  et  de  Physique,  3d  series,  vol.  18,  p.  5  (1909).  There 
is  a  German  translation  by  Donau  in  Kolloidchemische  Beihefte,  vol.  1,  p.  1 
(1910).  An  English  translation  by  Soddy  has  appeared  in  book  form  under 
the  title  "  The  Brownian  Movement  and  Molecular  Reality." 


Am.  Jour.  Pharm.  ) 
February,  1914.  J 


The  Starch  Grain. 


81 


These  are  only  two>  of  many  fundamental  results  contained  in  this 
wonderful  memoir.  Van't  HofT  extended  the  gas  laws  to  solutions. 
Perrin  has  now  proved  them  to  be  valid  for  systems  in  which  the 
moving  particles  are  visible  realities.  Let  us  end  by  quoting  one  of 
the  sentences  of  his  conclusion : 

"  ha  decouverte  de  telles  relations  marque  le  point  ou  s'eUve, 
dans  notre  conscience  scientiUque,  la  realite  moleculaire  sousjacente." 


THE  INFLUENCE  OF  HEAT  AND  CHEMICALS  ON  THE 
STARCH  GRAIN.1 
By  Henry  Kraemer. 

In  presenting  some  of  the  most  recent  observations  on  the  starch 
grain,  it  may  be  well  to  consider  for  a  moment  the  nature  and 
origin  of  starch.  In  a  way  starch  is  one  of  the  most  remarkable 
substances  produced  by  the  plant.  It  is  the  first  visible  product 
formed  by  the  chloroplastid,  or  chlorophyll  bodies,  from  the  inor- 
ganic substances,  carbon  dioxide  and  water.  Inasmuch  as  sunlight 
seems  to  be  necessary  to  bring  about  this  transformation  the  process 
is  looked  upon  as  one  which  involves  the  converting  of  the  sun's 
energy  into  vital  energy. 

The  substance  thus  formed  by  the  chloroplastid  through  the 
influence  of  sunlight,  in  the  leaves  and  other  green  parts  of  plants, 
is  known  as  "  assimilation  starch,"  and  serves  subsequently  not 
only  as  a  food  for  the  plant  itself  but  is  also  the  source  of  the 
energy  of  the  animal  world.  Assimilation  starch  is  not  stored  in 
the  cells  where  it  is  manufactured,  but  each  night  through  the 
influence  of  the  plant  ferments  the  starch  formed  during  the  day 
is  converted  into  a  soluble  form,  and  transported  to  various  other 
parts  of  the  plant.  In  some  cases  this  soluble  starch  is  tem- 
porarily stored  in  the  cells  of  the  pith,  medullary  rays,  or  bark, 
and  has  received  the  name  of  "  depot  starch."  While  some  of 
the  soluble  carbohydrate  is  converted  into  fixed  oils  and  other 
substances,  a  considerable  portion  of  it  is  carried  to  some  reserve 
organ,  as  a  root,  tuber,  rhizome,  or  seed,  and  under  the  influ- 
ence of  a  plastid  similar  to  the  chloroplastid,  converted  into  a 
stable  form,  known  as  reserve  starch. 

1  Reprinted  from  Original  Communications,  Eighth  International  Con- 
gress of  Applied  Chemistry.    Vol.  XVII — Page  31. 


82 


The  Starch  Grain. 


J  Am.  Jour.  Pharm. 
i    February,  1914. 


Ihis  is  the  product  with  which  we  are  specially  concerned  in 
the  present  article.  Hereto  t  ore,  the  minute  study  of  the  starch 
grain,  particularly  of  its  structure,  has  been  of  scientific  interest 
only,  but  with  the  application  of  scientific  methods  in  nearly  every 
department  of  industry,  it  is  coming  to  have  a  practical  application. 

The  commercial  reserve  starches  are  derived  from  various 
plants,  and  not  only  enter  largely  into  food  products  but  are  also 
used  for  a  variety  of  technical  purposes.  The  grains  of  the  re- 
serve starches  have  a  number  of  characteristic  features.  They 
vary  in  size,  in  shape,  in  internal  structure,  and  also  to  a  con- 
siderable extent  in  composition.  The  variation  in  composition  is 
shown  by  the  use  of  aniline  stain  and  also  by  the  use  of  iodine. 
By  the  treatment  of  starch  with  iodine  solution,  we  may  distinguish 
three  kinds  of  reserve  starch:  (i)  one  which  is  colored  deep  blue, 
as  potato  and  maranta;  (2)  one  which  is  colored  somewhat  purplish, 
changing  to  cinnamon-brown,  as  corn  and  wheat;  and  (3)  one 
which  is  colored  brownish-red,  as  in  the  amylo-dextrin  starches 
of  comfrey  and  a  few  other  plants. 

The  shape  of  the  grains  varies  from  polygonal  to  ellipsoidal, 
the  shape  being  influenced  by  the  number  of  grains  in  a  cell.  Under 
the  micro-polariscope  the  grains  are  seen  to  be  anisotropic,  the 
polarization  effects  differing  with  the  grains  of  the  different  classes. 
Polarizing  effects  are  usually  produced  by  crystals,  but  may  be 
produced  by  substances  in  a  condition  of  tension,  as  minute  globules 
of  glass.  It  should  also  be  stated  that  cell  walls  have  this  same 
property  of  double  refraction,  and  it  is  very  likely  that  the  sub- 
stances in  the  starch  grains,  as  well  as  in  the  cell  wall,  are 
crystalloidal  and  arranged  in  spherite  aggregates,  resembling  those 
of  inulin,  a  product  closely  resembling  starch. 

The  theories  which  have  been  advanced  regarding  the  struc- 
ture of  the  starch  grain,  have  been  largely  based  on  studies  of 
the  potato  starch  grain.  It  was  originally  thought  to  be  in  the 
nature  of  a  globule  filled  with  a  fluid.  Fritzche,  Schleiden  and 
others  considered  it  to  be  made  up  of  more  or  less  concentric 
layers  formed  around  a  central  or  excentral  point.  While  it  may 
be  true,  as  pointed  out  by  Naegeli,  that  many  of  the  reserve  and 
glucose  starch  grains  arise  free  in  the  cell,  the  view  of  Schimper 
that  starch  grains  always  develop  within  plastids,  is  generally 
accepted  at  the  present  time. 

The  internal  structure  of  the  starch  grain  is  shown  in  several 


Am.  jour.  Piiarm.  \ 
February,  1914.  J 


The  Starch  Grain. 


83 


ways.  When  starch  is  treated  with  certain  chemicals,  or  heated 
with  water  alone  to  a  temperature  of  6o°  C,  the  grains  show  a 
series  of  successive  changes.  First,  the  lamellae  or  layers  become 
more  distinct,  and  the  layers  appear  to  be  made  up  of  parallel 
crystal-like  particles,  these  latter  being  more  numerous  in  suc- 
cessive alternate  lamellae.  Then  as  the  grain  swells  clefts  which 
radiate  from  the  centre  are  formed.  Later  the  centre  of  the  grain 
becomes  hollow,  and  when  the  grain  has  swollen  to  about  four 
times  its  original  size  the  outer  membrane  breaks  and  the  con- 
tents are  gradually  dissolved. 

Some  striking  effects  are  also  produced  when  starch  is  carefully 
treated  with  aniline  dyes.  The  point  of  origin  of  growth  and  the 
successive  layers  alternating  with  it  take  up  the  stains,  thus  again 
showing  the  distinct  character  of  the  two  kinds  of  lamellae  making 
up  the  grains.  When  plant  material  containing  mucilage  is  treated 
with  aniline  stains,  the  stain  is  taken  up  only  by  the  cells  containing 
mucilage,  and  this  indicates  that  the  lamellae  in  a  starch  grain 
which  take  up  the  stains  are  composed  chiefly  of  colloidal  sub- 
stances. From  these  observations  it  is  apparent  that  the  grains 
of  certain  of  the  starches,  as  the  potato,  if  not  of  all  the  lamellated 
starch  grains,  are  made  up  of  two  kinds  of  lamellae,  one  rich  in 
colloids  and  one  rich  in  crystalloids.  The  presence  of  two  kinds  of 
lamellae,  at  least  in  certain  of  the  starch  grains,  and  their  difference 
of  composition  are  further  shown  by  the  use  of  a  weak  solution 
of  iodine,  the  so-called  crystalloidal  layers  or  lamellae  taking  up  the 
iodine  and  becoming  blue.2 

Recently  I  have  been  conducting  some  experiments  to  deter- 
mine further  the  effects  of  heat  upon  the  structure  of  the  starch 
grain.  When  starch  alone  is  heated  to  between  45 °  and  500  C.  from 
15  to  30  minutes,  the  lamellae  and  the  crystalloidal  structure  of  the 
grains  are  brought  out.  The  grain  is  so  resistent  that  the  inner 
structure  does  not  appear  to  be  lost  until  a  temperature  of  over 
1250  C.  is  attained.  Between  1400  and  1600  C.  the  polarization  effects 
of  the  grains  become  faint,  except  in  the  case  of  potato  starch, 
which  now  in  addition  gives  chromatic  effects.  At  2400  C.  all  of  the 
grains  are  disintegrated  except  those  of  corn  starch,  the  individual 
grains  of  which  are  of  a  brownish-yellow  color  and  not  perceptibly 


2Kraemer,  Bot.  Gazette,  Vol.  XXXIV,  Nov.,  1902 ;  Ibid.,  Vol.  XL,  Oct., 
1905;  reprinted  in  Amer.  Jour.  Pharm.,  Vol.  79,  1907,  pp.  217-229;  412-418. 


84 


The  Starch  Grain. 


{  Am.  Jour.  Pharm. 
V  February,  1914. 


swollen.  Besides  the  entire  mass  is  more  or  less  granular,  while 
in  the  case  of  the  other  starches  examined  the  charred  mass  is  in 
a  puffed  condition. 

The  effects  produced  when  starch  is  heated  in  the  presence 
of  a  fixed  oil,  as  almond  oil,  are  of  special  interest.  The  inner 
structure  of  the  starch  grain  is  not  usually  apparent  when  it  is 
mounted  in  a  fixed  oil,  unless  the  starch  has  been  previously  heated 
to  a  temperature  of  from  8o°  to  1600  C.  When,  however,  a  mixture 
of  starch  and  oil  is  heated  as  high  as  i8'o  C.  the  grains  still  polarize 
light,  which  shows  that  the  structure  has  not  been  altered.  In 
other  words  the  effects  of  heat  on  the  grain  are  more  or  less 
neutralized  by  the  presence  of  the  oil.  On  heating  the  mixture  up 
to  2500  C.  most  of  the  grains  still  show  their  individual  character, 
but  no  longer  polarize  light.  They  are  but  slightly  swollen,  and 
in  the  case  of  cassava  and  corn  starch  a  central  differential  area 
occupies  from  one-half  to  nine-tenths  of  the  original  area  of  the 
grain. 

It  may  be  worth  while  to  state  that  when  starch  and  water 
in  the  proportion  of  2  gm.  of  the  former  to  100  c.c.  of  the  latter, 
are  heated  together  at  a  temperature  of  between  900  and  ioo°  C. 
in  a  steam  sterilizer  seven  or  eight  hours  a  day  for  a  long  period, 
even  extending  to  months,  dextrinization  of  the  starch  does  not 
take  place,  that  is,  the  solution  still  gives  a  blue  color  with  iodine. 
Even  though  the  operation  be  conducted  in  an  autoclave  under 
a  pressure  of  20  pounds  for  about  ten  hours,  dextrinization  is 
not  effected.  If,  however,  1  c.c.  of  N/HC1  be  added  to  100  c.c. 
of  water  and  this  heated  for  five  hours  with  1  gm.  of  starch,  the 
resulting  solution  is  colored  red  with  iodine.  When  the  amount 
of  the  acid  is  reduced  to  .2  c.c.  and  the  mixture  heated  under 
a  pressure  up  to  12  pounds  for  one  hour,  cassava,  corn,  maranta 
and  potato  starch  solutions  give  a  deep  blue  color  with  iodine, 
while  a  solution  of  wheat  starch  gives  a  deep  purple  color  with 
iodine.  If  the  heat  be  continued  an  hour  longer,  wheat  starch 
gives  a  purplish-red  color,  cassava  a  deep  wine  color,  maranta 
and  potato  a  light  purple,  while  corn  still  gives  a  blue  reaction 
with  iodine. 

These  observations  may  be  summarized  as  follows : 
1.  The  starch  grain  consists  of  two  nearly  related  substances: 
(a)  a  colloidal  or  mucilage-like  substance  which  takes  up  aniline 


Am.  Jour.  Pharm.  ) 
February,  1914.  / 


Book  Reviews. 


85 


dyes,  and  (b)  a  crystalloidal  or  crystal-like  material  giving  a  blue 
color  with  iodine. 

2.  The  starch  grain  is  made  up  of  concentric  layers,  one  series 
of  which  contains  a  large  proportion  of  crystalloids,  while  the 
alternate  layers  are  composed  mostly  of  colloids. 

3.  The  polarization  effects  produced  by  starch  are  probably  to 
be  attributed  to  the  crystalloidal  character  of  the  grains. 

4.  The  starch  grains  retain  their  polarizing  properties  even  when 
heated  up  to  a  temperature  of  1800  C,  which  seems  very  remarkable 
indeed. 

5.  At  the  higher  temperatures  the  potato  starch  grains  give 
chromatic  effects  in  addition,  similar  to  those  when  a  selenite 
plate  is  used. 

6.  While  heating  the  starch  grains  in  water  rapidly  changes  the 
structure  of  the  grain,  it  is  only  by  the  addition  of  chemicals  or 
ferments  that  dextrinization  is  brought  about. 


BOOK  REVIEWS. 

Semi-Annual  Report  on  Essential  Oils,  Synthetic  Per- 
fumes, &c.  Published  by  Schimmel  &  Co.  (Fritzsche  Brothers), 
Miltitz  near  Leipzig.    London,  New  York.    October,  1913. 

In  the  introduction  to  this  report  an  admirable  resume  is  given 
of  conditions,  both  favorable  and  adverse,  which  affected  business 
in  the  last  year  and  particularly  as  to  commodities  handled  by  this 
firm. 

As  is  known  to  well-informed  pharmacists,  the  practice  of 
sophistication  is  found  in  many  branches  of  business  but  in  none 
so  much  as  in  the  essential  oil  industry.  In  fact,  one  is  almost  led 
to  believe  that  adulteration  of  oils  and  perfumes  is  an  industry  in 
itself.  Upward  movement  of  prices  is  the  dominant  cause  for  this, 
and,  as  is  always  the  way,  the  forces  of  evil  and  dishonesty  are  up 
and  doing,  and  "  the  practice  of  adulteration  is  assuming  dimen- 
sions, and  is  pursued  with  refinements  of  ingenuity  that  baffle  de- 
scription." So  cleverly  are  adulterants  selected  and  manipulated 
that  the  constants  of  an  adulterated  oil  are  kept  within  the  right 
limits  of  value  and  only  a  most  thorough  examination  will  show  the 
true  state  of  affairs.  Artificial  esters  play  an  important  part  in  this 
nefarious  work ;  for  instance,  when  added  to  oils  such  as  lavender 


86 


Book  Reviews. 


f  Am.  Jour.  Pharm. 
\  February,  1914. 


and  bergamot,  they  give  "  to  them  the  appearance  of  containing  far 
more  linalyl  acetate  than  the  oils  possess  in  reality." 

In  this  report  the  statement  is  made  that  there  are  firms  who  do 
not  hesitate  to  offer  such  esters  openly  for  purposes  of  adulteration. 
Furthermore,  it  is  stated  that  one  firm  made  such  an  offer  to  the 
Schimmel  people  in  writing  who  publish  this  communication  in  the 
original  language  and  a  translation  of  which  follows : 

Gentlemen  : 

For  some  years  past  we  have  been  in  the  habit  of  supplying  to 
lavender  growers  a  product  called  "  Ether  L." 

The  advantage  of  this  article  is  that  it  simulates  in  a  perfect 
manner  essential  oil  of  lavender,  and  we  have  judged  it  opportune 
to  forward  you  to-day  a  sample  of  it  by  post.  The  price  is  12.50 
francs  per  kilo  delivered  at  your  works. 

If  this  product  should  interest  you  by  any  chance,  please  let  us 
know  what  quantities  of  it  you  would  be  able  to  use  annually. 

Hoping  to  hear  from  you  we  are,  &c, 

N.  V.  Polak  &  Schwarz's, 

Essence  Fabrieken, 
Zaandam  ( Holland ) . 
P.  S. — Our  Ether  L.  is  pure  and  contains  100  p.  c< 
Subsequent  examination  of  this  product  showed  that  instead  of 
being  100  per  cent,  it  revealed  a  percentage  of  86.    The  presence  of 
this  ester  in  lavender  oil  would  not  prove  difficult  of  detection. 

The  high  price  of  menthol  also  proved  a  stimulus  to  those  of  dis- 
honest tendencies.  Two  samples  examined  showed  100  per  cent, 
adulteration.  Both  were  acetanilid,  one  scented  with  menthol  and 
the  other  with  peppermint  oil.  Under  the  name  Mentholin  there  is 
being  offered  to  the  trade  a  substitute  for  menthol  made  by  a  firm 
in  Prague  which  proved  to  be  80  per  cent,  acetanilid  and  oily 
menthol. 

This  report  consists  of  151  pages  of  interesting  matter,  the 
greater  part  of  which  is  devoted  to  commercial  notes  and  scientific 
information  pertaining  to  essential  oils ;  practically  every  oil  used  in 
pharmacy  and  in  the  manufacture  of  perfumery  is  touched  upon  as 
to  source  of  production,  supply,  and  conditions,  favorable  and  other- 
wise, which  may  have  had  some  influence  on  quality  or  lack  of 
quality. 

Considerable  attention  is  given  to  recent  scientific  research  in 


Am.  Jour.  Pharm.  ) 
February,  1914.  j 


Book  Reviews. 


87 


the  field  of  essential  oils.  Abstracts  of  reports  on  experimental  cul- 
tivation of  medicinal  plants  are  given,  a  field  of  endeavor  which 
must  be  nurtured  if  the  supply  of  drugs  is  to  keep  pace  with  the 
demand. 

Among  the  pages  of  this  report  are  several  excellent  pictures 
illustrative  of  the  essential  oil  industry.  One  is  a  particularly  strik- 
ing view,  in  color,  of  the  Miltitz  rose-fields  at  harvest  time. 

After  reading  over  this  report  and  digesting  the  information 
given,  one  cannot  help  but  feel  that  in  the  examination  of  an  oil 
(say  oil  of  rose)  and  in  which  the  other  constants  are  normal — a 
remarkably  high  ester  value  should  be  regarded  with  suspicion ! 

British  Pharmaceutical  Conference.  A  Presidential 
Survey  1863  to  1913.  Being  a  sketch  of  the  origin  and  progress 
•of  the  conference  prepared  on  the  occasion  of  the  celebration  of  its 
jubilee  in  London,  July  21  to  25,  1913.  The  Chemist  and  Druggist, 
42  Cannon  Street,  London. 

This  handy  little  volume  of  96  pages  contains  concise  but  inter- 
esting biographies  of  the  various  men  who  have  been  honored  by  the 
presidency  of  the  British  Pharmaceutical  Conference. 

In  the  fifty  years  of  its  existence  the  Conference  has  been  guided 
by  thirty-three  presidents,  all  men  of  ability  and  some  of  rare  scien- 
tific attainments.  Among  the  list  of  names  two  stand  out  in  bold 
relief — Hanbury  and  Attfield.  These  two  names  are  probably  more 
familiar  to  workers  in  pharmacy  in  this  country  than  any  other  two 
from  other  lands.  Hanbury  won  an  enviable  position  in  the  world 
of  science  by  his  work  as  a  pharmacognocist.  He  will  also  be  remem- 
bered as  the  donor  of  the  Hanbury  Medal.  This  is  only  given  to 
men  who  have  done  something  and  our  own  Professor  Maisch  was 
the  first  American  to>  receive  this  signal  honor.  And  Attfield,  we 
think  few  American  students  are  unfamiliar  with  the  book  on  chem- 
istry bearing  that  name,  with  its  many  chemical  experiments  which 
the  student  is  advised  to  perform.  He  impressed  on  the  student 
the  fact  that  the  way  to  study  chemistry  was  to  work  at  it. 

John  K.  Thum. 

Payne's  Dictionary  of  Pharmacy.  By  George  F.  Payne, 
Ph.G.,  M.D.,  F.C.S.    Published  by  G.  F.  Payne,  Atlanta,  Ga. 

Lack  of  space  forbids  us  to  give  the  full  title  given  by  the  author 
to  this  little  handbook  of  pharmaceutical  facts.    For  the  same 


88 


Book  Reviews. 


f  Am.  Jour.  Pharm. 
\  February,  1914. 


reason  we  are  compelled  to  omit  mention  of  the  numerous  offices 
and  honors  the  distinguished  writer  has  been  honored  with  and 
which  he  mentions  on  page  one.  It  suffices  to  say  that  he  is  "  an 
active  pharmacist  for  51  years";  that  the  little  volume  is  copy- 
righted, and  all  rights  are  reserved,  whatever  that  may  mean. 

We  have  been  rather  hopeful  that  the  day  of  cramming  books 
was  over,  but  this  short-cut  to  the  study  of  pharmacy  and  allied 
branches  seems  like  evidence  to  the  contrary. 

The  study  of  a  science  and  art  like  pharmacy  by  the  "  absorp- 
tion "  of  isolated  facts  is  a  survival  of  the  day  when  the  unschooled 
errand  boy  of  the  retail  drug  store  developed  into  a  clerk  and  squeezed 
through  a  board  of  pharmacy  examination  by  heroically  attempting 
to  memorize  the  dispensatory.  In  the  past,  board  of  pharmacy  ex- 
aminations consisted  very  much  of  "  catch  "  questions  and  a  student 
expected  them  and  prepared  for  them  ;  if  he  answered  them  correctly 
the  board  assumed  that  he  was  fit  to  practise  pharmacy ;  all  of  which 
was  not  conducive  to  the  best  interests  of  the  public  and  cer- 
tainly lowered  the  level  of  the  profession.  Indeed,  the  inefficiency 
of  many  pharmacists,  who  must,  because  of  such  inefficiency,  depend 
upon  manufacturing  houses  for  many  pharmaceuticals  that  they 
should  make  themselves,  can  be  traced  to  this  method  of  education 
or  lack  of  education  in  their  chosen  profession. 

Happily,  in  the  larger  centres  of  our  country  there  is  beginning 
to  manifest  itself  by  the  public  a  demand  for  a  higher  type  of  man 
for  the  professions,  ours  included.  And  this  demand  is  being  met 
and  complied  with  by  the  better  class  of  schools  with  more  stringent 
requirements  as  to  preliminary  education  and  a  broadening  of  the 
curriculum.  This  is  as  it  should  be,  and  in  the  evolution  of  things 
schools  of  other  centres  must  do  likewise  or  cease  to  exist. 

John  K.  Thum. 

Materia  Medica,  Pharmacology,  Therapeutics,  Prescrip- 
tion Writing,  for  Students  and  Practitioners.  By  Walter  A. 
Bastedo,  Associate  in  Pharmacology  and  Therapeutics  at  Columbia 
University,  etc. 

This  book,  which  is  from  the  press  of  the  W.  B.  Saunders  Co., 
is  a  medium  8vo.  in  size,  of  602  pages,  price  $3.50  net.  It  is  an  ex- 
cellent specimen  of  the  book-making  art,  the  binding  and  paper 
being  excellent,  the  type  clear  and  distinct. 


Am.  Jour.  Pharm.  ) 

February,  1914.  J 


Book  Reviews. 


89 


The  work  is  original  in  many  respects,  not  following  the  beaten 
path,  and  has  in  it  much  to  commend. 

It  is  divided  into  three  parts,  Part  I  being  largely  by  way  of  in- 
troduction. Among  some  of  the  subjects  considered  in  this  divi- 
sion are :  Pharmaceutical  preparations ;  Weights  and  measures ; 
Active  principles ;  The  Pharmacopoeia ;  Dosage,  Administration  of 
medicines,  etc. 

Part  II  treats  of  materia  medica  proper.  Many  of  the  classifi- 
cations are  different  from  other  books  on  this  subject,  one  of  them 
being  Sweetening  Agents,  which  includes  saccharin,  which  he 
states  "  has  been  much  employed  in  canning  foods,  as  it  is  slightly 
antiseptic  and  obviates  the  use  of  the  highly  fermentable  sugar." 
This  seems  to  be  flying  directly  in  the  face  of  Dr.  Wiley.  The  Anti- 
Bitters  are  claimed  to  abolish  the  appreciation  of  bitter  tastes ;  these 
include  yerba  santa  and  gymnemic  acid.  The  list  of  cathartics  in- 
clude those  which  act  by  "  selective  affinity,"  as  physostigmine,  which 
stimulates  the  ends  of  the  vagus  nerves  of  the  intestines.  A  new 
classification  is  given  to  the  Antispasmodics,  they  being  called  the 
Antihysterics. 

The  classification  of  the  Antipyretics  is  somewhat  original.  We 
have  the  analgesic  antipyretics,  such  as  antipyrin,  the  antimalarial 
antipyretics,  such  as  cinchona ;  and  the  antirheumatic  antipyretics, 
such  as  salicylic  acid. 

The  article  on  the  thyroid  gland  is  interesting  and  of  value,  a  new 
classification  being  called  the  Antithyroid  preparations,  designed  to 
overcome  undue  activity  of  the  thyroid  gland,  the  remedies  included 
under  this  head  being  Beebe's  serum;  Antithyroidin  (Moebius),  and 
Thyroidectin.  Antithyroidin  is  the  blood  serum  obtained  from  sheep 
whose  thyroid  glands  have  been  removed,  at  least  six  weeks  before. 

The  therapeutic  classification  of  the  Disinfectants  is  also  original 
and  valuable.  It  includes  I,  The  general  disinfectants  and  deo- 
dorizers ;  II,  The  preservatives ;  III,  Disinfectants  for  surgical  sup- 
plies ;  IV,  Disinfectants  for  local  use  about  the  body ;  V,  Disinfect- 
ants to  be  given  by  the  mouth.  The  important  drugs  of  the  materia 
medica  are  treated  of  at  considerable  length,  digitalis  having  42 
pages  assigned  to  it,  and  epinephrine  (adrenalin)  ten  pages.  In 
the  article  on  digitalis,  it  is  stated  that  "  digitalis  contains  digitonin,  a 
saponin  body  which  foams  with  water  and  possesses  the  peculiar 
property  of  holding  the  otherwise  insoluble  active  principles  in  solu- 
tion in  water.    It  is  on  account  of  this  that  infusion  of  digitalis,  an 


go 


Book  Reviews. 


f  Am.  Jour.  Pharm. 
[  February,  1914. 


aqueous  preparation,  represents  the  activity  of  the  drug."  While 
this  is  somewhat  different  from  what  we  have  heretofore  believed,  it 
does  not  justify  the  making  of  the  infusion  from  a  fluidextract,  as 
digitonin  is  not  soluble  in  an  alcoholic  menstruum,  and  such  an  infu- 
sion would  not  contain  any  digitonin,  and  the  glucosides  insoluble 
in  water  would  not  therefore  be  held  in  solution. 

The  book  is  up-to-date  in  the  introduction  of  new  remedies,  a 
few  only  being  cited,  such  as  Hormonal  from  the  spleen  of  the 
rabbit,  which  is  stated  to  be  "  of  value  in  post-operative  tympanites 
and  obstinate  chronic  constipation."  Oxyntin  and  Acidol  are  albu- 
minous forms  of  hydrochloric  acid.  The  chapter  on  Hypnotics  is  of 
interest,  especially  the  contrast  between  natural  sleep  and  that  in- 
duced by  the  aid  of  drugs. 

"  The  article  on  tobacco  will  be  read  with  interest,  as  the  author 
seems  to  think  "  that  the  demand  for  tobacco  is  not  so  much  the 
physiological  demand  of  the  body  for  its  dose  of  nicotine,  as  it  is  the 
psychic  demand  for  the  satisfaction  of  a  habit." 

He  thinks  that  pepsin  "  in  almost  all  cases  of  digestive  disturb- 
ance is  a  superfluous  remedy,"  but  that  pancreatin  is  of  greater 
value.  In  fact,  he  gives  some  remarkable  instances  of  its  effects  in 
the  case  of  arrested  development,  one  of  which  was  a  boy  who  grew 
five  inches  in  two  years  and  gained  twenty-two  pounds.  He  is  op- 
posed to  the  prescribing  of  mixtures  of  the  digestive  ferments  to- 
gether, as  frequently  they  destroy  each  other.  Of  aconite  which 
has  been  the  sheet  anchor  of  Homeopathy  for  so  many  years,  is 
asserted,  "  that  in  the  light  of  recent  research  has  doubtful  thera- 
peutic value."  Camphor  cerate  is  not  "  camphor  ice  "  as  stated,  the 
latter  being  the  Compound  cerate  of  the  N.  F.  Jalap  is  said  to 
contain  8  per  cent,  of  resin,  the  amount  should  be  given  as  7  per 
cent.  The  doses  as  given  in  the  work  vary  considerably  from  those 
of  the  pharmacopoeia.  Under  the  head  of  reflex  emetics,  the  dose  of 
copper  sulphate  is  stated  as  thirty  grains,  the  pharmacopoeia  gives 
it  as  four  grains,  that  of  tartar  emetic  as  two  grains,  the  official  dose 
is  y^t  g. ;  we  have  same  unpleasant  remembrances  of  the  effects  of  a 
one-grain  dose  of  tartar  emetic.  The  dose  of  sparteine  sulphate  is 
given  as  one  grain,  which  is  probably  nearer  correct  than  the  dose 
given  in  the  Pharmacopoeia.  The  dose  of  all  the  mydriatic  alkaloids 
(as  atropine)  and  their  salts  is  stated  as  the  1/150  grain,  no  varia- 
tion between  them  being  given. 

Apomorphine  hydrochloride  is  cited  as  being  the  only  central 


rtSS,?™'}     Philadelphia  College  of  Pharmacy.  91 

(systemic)  emetic,  other  authorities  include  tartar  emetic,  senega  and 
squill. 

Part  III  is  devoted  to  Prescription  Writing,  which  the  author 
states  "  is  the  dread  of  the  young  medical  practitioner."  This  part, 
while  brief,  is  quite  practical,  and  may  be  of  considerable  value  in 
starting  the  young  practitioner  aright,  but  what  he  should  have  to 
make  him  an  expert  in  the  art  of  prescription  writing  is  a  more  ex- 
tensive practice  while  in  college.  Much  of  the  fourth  year  in  college 
could  be  devoted,  directly  or  indirectly,  to  this  work,  and  then  the 
young  physician  would  be  able  to  use  his  knowledge  of  materia 
medica  intelligently  and  practically.  In  conclusion,  we  would  state 
that  we  have  examined  the  book  with  much  interest,  and  shall  have 
pleasure  and  profit  in  consulting  its  pages  in  the  future;  it  is  well 
worthy  of  being  added  to  every  physician's  library. 

C.  B.  Lowe,  M.D. 


PHILADELPHIA  COLLEGE  OF  PHARMACY. 
Minutes  of  the  Quarterly  Meeting. 

The  quarterly  meeting  of  the  Philadelphia  College  of  Pharmacy 
was  held  December  29th,  19 13,  at  4  p.m.,  in  the  Library.  The  Presi- 
dent, Howard  B.  French,  in  the  Chair.  Sixteen  members  present. 
The  minutes  of  the  semi-annual  meeting  held  September  29th  were 
read  and  approved.  The  minutes  of  the  Board  of  Trustees,  for  the 
meetings  held  September  2-16,  October  7,  and  November  5,  were 
read  by  the  Registrar,  J.  S.  Beetem,  and  approved. 

Acknowledgments  of  having  received  notice  of  their  election  to 
Honorary  Membership  were  received  from  Doctors  Carl  L.  Alsberg 
and  A.  L.  Winton. 

The  President  reappointed  the  following  as  the  Committee  on 
Legislation :  Warren  H.  Poley,  Joseph  P.  Remington,  Theodore 
Campbell,  William  E.  Lee,  William  L.  Cliflfe,  Richard  H.  Lackey. 

C.  A.  Weidemann,  M.D., 

Recording  Secretary. 

Abstracts  from  the  Minutes  of  the  Board  of  Trustees. 


September  16th:  Thirteen  members  present.  The  Committee 
on  Property  reported  that  the  Library  ceiling  had  been  repaired, 
woodwork  cleaned  and  varnished,  new  carpet  (cork)  put  down, 


92  Philadelphia  College  of  Pharmacy.  {Veb™£,^™" 

and  new  chairs  purchased.  Also  that  the  woodwork  of  the  lower 
front  of  the  College  had  been  painted,  that  changes  had  been  made 
in  the  lower  Microscopical  Laboratory,  and  that  the  Gymnasium 
had  been  put  in  first  class  condition. 

The  Finance  Committee  approved  the  recommendation  that 
Prof.  Moerk  engage  the  services  of  two  student  assistants  and  Prof. 
Kraemer  one  student  assistant  for  the  College  term. 

The  Committee  on  Appropriations  approved  the  estimated 
amounts  that  would  be  required  by  the  several  committees  and  de- 
partments authorized  to  make  expenditures. 

The  Committee  on  Scholarships. — The  Chair  reported  that  owing 
to  the  absence  of  the  Dean  in  Europe,  it  was  necessary  to  act  on  the 
applications  presented  at  the  October  meeting  of  the  Board  and 
suggested  that  the  Assistant  Dean  be  placed  on  the  Scholarship 
Committee  in  the  interim.    It  was  so  ordered. 

The  Joint  Committee  on  Instruction  and  Examination  made  a 
report  relative  to  students  taking  the  course  in  Bacteriology,  which 
was  adopted. 

The  Committee  on  Examinations  reported  that  John  L.  Bush, 
Harry  C.  Cowles,  and  Paul  A.  Kind,  having  complied  with  all  th^ 
requirements,  were  recommended  to  receive  the  Certificate  of  Pro- 
ficiency in  Chemistry ;  and  that  Roy  L.  Clark  having  complied  with 
all  the  requirements  was  recommended  to  receive  the  Certificate  of 
Proficiency  in  Food  and  Drug  Analysis.  These  recommendations 
were  approved. 

The  Committee  on  Announcement  reported  the  regular  issuance 
of  the  Bulletin. 

A  letter  was  read  from  the  Secretary  of  the  State  Pharmaceutical 
Board  relative  to  the  fact  that  the  highest  ratings  of  those  who  ha  1 
taken  the  June  examinations  had  been  bestowed  upon  two  graduates 
of  the  Philadelphia  College  of  Pharmacy. 

Mr.  French  referred  to  the  honor  conferred  upon  Dr.  F.  B. 
Power,  a  graduate  of  the  College,  who  had  been  awarded  the 
Hanbury  Gold  Medal,  and  he  suggested  that  a  letter  of  congratula- 
tion be  sent  Dr.  Power.  This  met  with  hearty  approval  and  the 
suggestion  was  adopted. 

An  application  for  active  membership  was  received  and  referred 
to  the  Committee  on  Membership. 

The  Treasurer's  Annual  Report  was  received,  and  referred  to 
the  Committee  on  Accounts  and  Audit. 


ASb™ary,Pih9T'}     Philadelphia  College  of  Pharmacy.  93 

October  7th:  Thirteen  members  present.  A  communication 
was  received  from  the  Recording  Secretary  of  the  College  report- 
ing the  election  of  E.  M.  Boring,  Charles  Leedom,  and  Theodore 
Campbell  to  membership  in  the  Board  of  Trustees  for  the  ensuing 
three  years. 

The  Committee  on  Property  reported  that  the  back  hall  and 
stairway  had  been  painted  and  put  in  good  condition. 

The  Committee  on  Library  reported  that  up  to  this  time  5246 
books  had  been  classified,  accessioned  and  shelf -listed. 

Donations  of  books  had  been  received  from  H.  G.  Kalmbach, 
Mrs.  Wm.  Mclntyre,  Professor  C.  B.  Lowe,  Professor  Henry 
Kraemer  and  the  Surgeon's  General  Office.  A  number  of  books 
had  been  purchased.   Fifty-two  persons  had  used  the  Library. 

The  Committee  on  Instruction  reported  that  several  students 
had  removed  conditions,  and  that  several  others  still  had  con- 
ditions to  be  removed,  and  suggested  rules  to  govern  such  cases  in 
the  future;  also  that  Prof.  Kraemer  had  selected  Anton  Hogstad, 
a  third  year  student,  as  an  assistant. 

The  Chairman  stated  that  Professor  Roddy  had  requested 
Messrs.  Mulford  &  Company  and  Parke,  Davis  &  Company  to  pre- 
sent samples  of  Bacteriological  products  to  his  laboratory,  with 
which  request  they  had  complied  and  new  products  would  ac- 
cordingly be  added.  The  thanks  of  the  Board  was  conveyed  to 
the  donors. 

The  Committee  on  Scholarships  reported  the  names  of  twelve 
persons  to  whom  scholarships  had  been  awarded. 

Mr.  Shoemaker  read  a  communication  from  Prof.  Kraemer 
to  the  Registrar  relative  to  the  fund  started  by  the  classes  ending 
in  4  and  9,  to  the  effect  that  the  fund  be  placed  in  the  hands  of 
the  Treasurer.  The  Treasurer  suggested  that  the  fund  be  one 
representing  all  graduates.  Prof.  Kraemer  was  requested  to  out- 
line the  plan  undertaken  by  the  classes  and  to  submit  such  out- 
lined plan  at  the  next  meeting  of  the  Board. 

An  application  for  Associate  Membership  was  received  and 
referred  to  the  Committee  on  Membership. 

The  Committee  on  Membership  reported  favorably  on  the  ap- 
plication of  George  L.  Sbntag,  of  Neillsville,  Wisconsin,  Class  of 
1890.   A  ballot  was  taken  and  he  was  unanimously  elected. 

November  5th:  Thirteen  members  present.  Committee  on 
Library  reported  an  additional  number  of  books  accessioned,  classi- 
fied and  shelf-listed  and  that  a  gift  had  been  received  from  G. 
Mason  Thompson.  A  number  of  books  had  been  purchased.  One 
hundred  and  forty-six  persons  had  used  the  Library. 


94  Philadelphia  College  of  Pharmacy.     { VeJuarj/ifi1' 

Committee  on  Instruction  reported  that  the  Sub-Committee  on 
Special  Lectures  had  secured  outside  talent  to  deliver  nine  special 
lectures  during  the  College  term.  A  wide  range  of  subjects  having 
been  selected.  Several  joint  meetings  of  the  Committees  on  Instruc- 
tion and  Examinations  were  held  to  formulate  some  system  of 
grading  or  evaluation  to  be  attached  to  the  results  of  the  examina- 
tions in  the  various  branches  of  the  College — such  system  that 
differentiates  between  the  Major  and  Minor  branches.  After 
earnest  consideration,  a  plan  has  been  proposed  by  which  each  sub- 
ject of  instruction  will  be  given  a  rating  corresponding  with  its 
importance.  This  plan  will  be  put  in  force  for  the  present  year  in 
order  that  its  adaptability  to  the  conditions  now  existing  may  be 
tested. 

The  Secretary  announced  that  he  had  received  letters  from  the 
recipients  of  scholarships  expressing  their  appreciation. 

The  Chairman  read  a  letter  from  Dr.  F.  B.  Power  expressing 
his  appreciation  of  the  good  wishes  and  congratulations  extended 
him  by  the  College.  The  correspondence  was  directed  to  be  pub- 
lished in  the  American  Journal  of  Pharmacy. 

Philadelphia  College  of  Pharmacy. 

September  Twenty-third,  19 13. 

Dr.  Frederick  B.  Power, 

Snow  Hill,  London,  E.  C,  England. 

Dear  Doctor : 

The  news  that  the  Committee  on  Hanbury  Medal  of  the  Pharma- 
ceutical Society  of  Great  Britain  had  awarded  you  this  year  this 
coveted  medal,  has  been  received  by  the  members  of  the  Philadelphia 
College  of  Pharmacy  with  mingled  feelings  of  pleasure  and  pride. 
It  is  now  nearly  forty  years  since  your  first  scientific  papers  were 
published  in  our  Journal  and  we  appreciate  that  with  the  harvest 
of  material  that  is  yours,  you  still  remember  us.  It  is  but  natural 
on  an  occasion  of  this  kind,  being  probably  the  proudest  in  your 
life,  that  we  in  offering  you  our  felicitations  and  congratulations 
should  remind  you  that  the  successive  steps  in  your  career  since 
graduating  from  our  College  and  working  in  its  faculty,  have  been 
followed  by  us  with  increasing  interest  as  year  by  year  has  passed. 
Rarely  does  it  fall  to  the  lot  of  any  one  man  to  accomplish  so  much, 
and  it  is  even  more  unusual  for  him  to  receive  while  yet  in  his  prime, 
the  recognition  he  deserves  for  the  days  and  nights  of  unremitting 


Areb^uaJy,Pih9ai4m'}     Philadelphia  College  of  Pharmacy.  95 

toil  with  which  he  has  applied  himself  to  his  chosen  task.  We  trust 
that  you  may  be  spared  many  years  to  continue  your  studies,  and  it 
is  our  earnest  desire  that  the  harvest  may  satisfy  your  proudest  hopes 
and  highest  expectations.  We  wish  you  health  that  you  may  work 
easily  as  well  as  effectively  and  enjoy  the  fruits  of  your  labors. 

Very  truly, 

Howard  B.  French, 

President. 

The   Wellcome   Chemical   Research  Laboratories, 
Frederick  B.  Power,  Ph.D.,  LL.D.,  Director. 

6,  King  Street,  Snow  Hill,  London,  E.  C. 

13  October,  1913. 

Howard  B.  French,  Esq., 

President,  Philadelphia  College  of  Pharmacy, 
Philadelphia,  Pa. 

Dear  Mr.  French : 

It  has  given  me  exceptional  pleasure  to  receive  your  very  kind 
letter  of  the  24th  ultimo,  and  1  desire  to  assure  you  of  my  deep 
appreciation  of  the  cordial  sentiments  and  good  wishes  therein 
expressed. 

The  significance  of  the  honor  attending  the  award  of  the  Han- 
bury  Gold  Medal  has  been  greatly  enhanced  to  me  by  the  feeling 
that  its  bestowal  has  also  afforded  gratification  and  pleasure  to  so 
many  of  my  esteemed  friends  across  the  sea.  The  occasion  of  its 
presentation  on  October  1st  was  a  memorable  one,  and  it  was  a 
great  delight  to  me,  as  indeed  to  the  entire  assembly,  that  Professor 
Remington  could  be  present  and  participate  in  the  proceedings.  His 
remarks  in  seconding  a  vote  of  thanks,  proposed  by  Sir  William 
Tilden,  F.R.S.,  for  my  address,  were  most  felicitous,  and  it  was  al- 
together a  grand  and  happy  day. 

I  have  been  deeply  touched  by  the  expressions  of  interest 
manifested  in  my  career  by  the  Philadelphia  College,  which  has 
indeed  been  to  me  a  "  kindly  mother."  I  am  grateful  for  the  stimu- 
lus to  scientific  study  which  was  first  received  as  a  student  within 
its  walls,  and  appreciate  very  highly  the  honors  it  has  in  later  years 
conferred  upon  me. 

In  heartily  reciprocating  your  good  wishes  for  health  and  hap- 
piness, believe  me  to  be, 

Sincerely  yours, 

Frederick  B.  Power. 


96  Philadelphia  College  of  Pharmacy.  {Afebm^i^' 

The  Committee  on  Membership  reported  favorably  on  the  ap- 
plication of  Otto  Raubenheimer,  of  Brooklyn,  N.  Y.,  as  an  As- 
sociate Member.  A  ballot  was  taken  and  he  was  unanimously 
elected. 

PHARMACEUTICAL  MEETINGS. 

The  second  Pharmaceutical  meeting  was  held  on  Friday  after- 
noon, November  14,  Mr.  Edward  M.  Boring  presiding. 

Prof.  Charles  H.  LaWall  presented  a  paper  on  "  Detection  of 
Chicory  in  Decoctions  of  Chicory  and  Coffee  "  prepared  in  conjunc- 
tion with  Mr.  Leroy  Forman. 

Mr.  Boring  then  exhibited  two  specimens  of  Elixir  of  Iron,  Qui- 
nine and  Strychnine,  made  six  months  apart,  their  fine  appearance 
being  due  to  neutralization  after  the  addition  of  the  iron  phosphate. 

Prof.  Remington  gave  a  delightful  talk  on  "  Some  Pharmaceutical 
Celebrities  I  Have  Met,"  in  connection  with  which  he  showed  a  large 
number  of  slides  including  portraits  and  views  in  laboratories  abroad 
and  in  manufacturing  houses. 

OBITUARY. 

Evan  Tyson  Ellis  was  born  in  Philadelphia  on  August  10,  1826 
and  died  in  the  same  city  on  October  11,  1913.  He  was  the  oldest 
alumnus  and  member  of  the  Philadelphia  College  of  Pharmacy,  the 
last  surviving  charter  member  of  the  Philadelphia  Photographic 
Society,  and  for  many  years  a  prominent  figure  in  the  wholesale  drug 
circles  of  Philadelphia. 

Mr.  Ellis  came  of  sturdy  Quaker  stock,  his  father,  Charles  Ellis, 
being  a  well  known  Orthodox  Quaker,  a  leading  wholesale  druggist 
and  an  official,  in  various  capacities,  of  the  Philadelphia  College  of 
Pharmacy  for  more  than  forty  years.  He  received  his  education  at 
Haverford  College  from  which  he  was  graduated  with  the  class  of 
1844  and  was  one  of  the  oldest  members  of  the  Haverford  College 
Alumni  Association.  He  then  studied  pharmacy,  attended  the  courses 
of  instruction  at  the  Philadelphia  College  of  Pharmacy,  graduating 
with  the  class  of  1847.  The  subject  of  his  thesis  was  "  Extract  of 
Valerian." 

After  he  was  graduated,  Mr.  Ellis  went  into  partnership  with  his 
father,  Charles  Ellis,  in  Philadelphia,  and  together  they  built  up  a 
large  wholesale  drug  business,  under  the  name  of  Charles  Ellis,  Son 
and  Co.  During  the  Civil  War  he  served  in  the  Hospital  Department 
of  the  U.  S.  Army. 

J.  W.  England. 


the  ameeica: 
JOURNAL  OF  PU^lM^y 

MARCH,  1914  Vir^  ^ y    ^ ^ 

DISTRIBUTION  OF  ALKALOIDS  IN  THE,B^LAD©NNA} | 

PLANT.*  VX^e^  <CJ 

By  A.  F.  Sievers,  Chemical  Biologist, 
Office  of  Drug  Plant  Investigations;  Bureau  of  Plant  Industry. 

In  connection  with  an  investigation  of  the  individual  variation 
of  the  alkaloidal  content  of  belladonna  plants,  it  was  desirable  to 
determine  the  relative  distribution  of  the  alkaloids  in  the  plant.  In 
this  article  are  presented  the  results  of  a  complete,  detailed  examina- 
tion of  a  number  of  such  individual  plants.  The  conclusions  that  may 
be  drawn  from  these  results  are  interesting  in  that  they  indicate  a 
number  of  facts  concerning  the  relative  therapeutic  value  of  various 
parts  of  the  plant  which  may  be  of  economic  significance.  Further- 
more, a  definite  knowledge  of  such  a  distribution  may  eventually 
add  to  our  information  concerning  the  role  of  the  alkaloids  in  the 
physiological  processes  of  the  plant. 

In  determining  the  alkaloids  it  was  frequently  necessary  to  assay 
very  small  samples.  The  method  employed  was  that  of  the  U.  S. 
Pharmacopoeia  with  some  modifications  of  the  technique  to  make 
the  process  applicable  to  small  samples.  These  modifications  have 
been  described  in  some  previous  articles.1  Analyses  were  made  of 
first  and  third  year  plants. 

Third- Year  Plants. 

The  analyses  of  the  third-year  plants  were  made  in  June,  when 
they  were  in  full  bloom.  Owing  to  the  fact  that  most  of  these 
were  reserved  for  other  work,  only  four  individual  plants  could  be 


*  Published  by  permission  of  the  Secretary  of  Agriculture. 
1  Merck's  Report,  August,  1910,  p.  215;  Journal  of  the  American  Pharma- 
ceutical Assn.,  March,  1912,  p.  199. 

(97) 


98 


Alkaloids  in  Belladonna  Plant. 


J  Am.  Jour.  Pharm. 
X     March,  1914. 


secured  for  the  experiment,  but  these  four  were  typical  of  the 
entire  plot. 

The  green  or  aerial  portion  of  each  plant  was  separated  into  the 
following  parts:  (i)  Flowers,  (2)  flowering  tops,  (3)  small  and 
large  leaves,  and  (4)  small  and  large  stems.  All  the  parts  were  im- 
mediately weighed  so  that  the  percentage  of  moisture  could  be  de- 
termined. The  flowers  included  only  the  open  flowers.  The  flower- 
ing tops  consisted  of  the  tops  of  the  branches,  including  about  three 
or  four  inches  of  the  young  stems  and  the  small  and  young  leaves 
and  flower  buds.  The  small  leaves  were  mostly  of  the  younger 
growth,  located  largely  near  the  upper  part  of  the  plant;  a  few, 
however,  growing  at  the  juncture  of  the  old  leaves  and  the  stems. 
The  large  leaves  were  picked  close  to  the  stem,  and  the  petioles 
at  the  base  of  the  leaves  were  removed  and  kept  separate.  The  large 
stems  were  separated  from  the  small  ones,  the  latter  including 
those  above  the  point  where  the  large  stem  forks.  The  small  stems 
as  a  rule  were  quite  small  and  tender,  averaging  about  a  quarter  of 
an  inch  in  diameter.  The  large  stems  were  split,  the  thin  bark 
peeled  off,  and  the  pith,  which  constitutes  the  bulk  of  the  interior 
of  the  stem,  was  scraped  out.   Each  part  was  weighed  separately. 

The  roots  were  carefully  dug  out  and  thoroughly  washed  to  re- 
move all  dirt.  The  small  roots,  which  consisted  mainly  of  the  young 
slender  ends  of  the  tap  roots  and  secondary  fibrous  roots,  were  then 
separated  from  the  large  ones.  The  large  roots,  or  thick  tap  roots, 
were  separated  into  two  parts,  the  wood  and  the  bark. 

After  being  thoroughly  air-dried,  all  parts  of  the  plants  were 
dried  to  constant  weight  in  a  hot-air  oven  at  a  maximum  temperature 
of  60  degrees  C.  The  alkaloids  were  determined  by  the  method  de- 
scribed, and  the  results  of  the  analysis  of  each  of  the  four  plants 
are  shown  in  Table  I,  which  is  summarized  at  the  close,  in  order 
to  compare  the  percentages  of  alkaloids  in  the  several  parts  of  the 
individual  plants. 

First- Year  Plants. 

There  were  six  of  the  first-year  plants,  and  these  were  analyzed 
in  September,  when  the  flowering  was  over  and  all  but  a  few  of 
the  berries  were  ripe.  The  serial  portion  of  each  plant  was  separated 
into  the  following  parts:  (1)  Small  and  large  leaves,  (2)  young 
sprouts,  (3)  fruit,  (4)  small  and  large  stems.  The  fruits  or  berries 
were  picked  with  the  stem  and  calyx  attached,  the  latter  being  after- 


Alkaloids  in  Belladonna  Plant.  99 
Table  I. 


A  nalyses  of  Four  Typical  Third-year  Belladonna  Plants. 


Plant  and  part 

Weight  (grams) 

Moist- 
ure 
per 

cent. 

Per 
cent,  of 
entire 
plant 

Alkaloids 

Green 

Dry 

Grams 

Per 
cent. 

Percentage 
of  quantity 

of  alka- 
loids in  the 
plant 

Plant  No.  1. 

Flowers  

Flowering  tops   . 

Leaves : 

Small  

Large : 

Without  petioles . 

Petioles  

Entire    1  arge 
leaves  

Total  

Stems: 

Small  

Large  : 

Pith  

Bark  

Wood  

Entire  large 

Total  

Roots: 

Small  

Large : 

Wood  

Bark  

Entire  large 
roots  

Total  

Entire  plant  

34-15 
194.20 

5-75 
31-94 

83-I7 
83-57 

2.14 

11 .86 

O.O255 
•2753 

0-445 
.862 

2  .27 
24.42 

40.36 

187.44 
28.94 

216.38 

7-55 

31.04 
2.89 

33-93 

82.68 

83-42 
9O.OO 

84.3O 

2.81 

n.56 
1.07 

12  .60 

.0512 

"73 
.OIIO 

.1283 

.679 

•378 
■381 

.378 

4-54 

10 .40 
•97 

11-37 

256.74 

41.48 

83.70 

I5-70 

-1795 

•432 

15.90 

161.65 

141 .80 
95.20 
113 .00 

350 .00 

20.33 

10 .00 
10.76 
27.81 

4°  -57 

87.40 
92.95 

87-93 
75-45 

86.10 

7-55 

3-71 
3-99 
10.33 

18  .04 

.0896 

•0337 
.0131 
.0292 

.0760 

.441 

-337 
.128 
-105 

-156 

7-93 

2.98 
1 .16 
2-59 

6  -73 

51165 

68.90 

86.58 

25-59 

.1656  .237 

14 .66 

85 -95 

473-30 
271 .70 

750.00 

13-81 

64-35 
42.95 

107 .30 

83  .92 

86.42 
84.20 

85.60 

5  •  13 

23.90 
15-95 

39.88 

.0701 

.2786 
•1331 

4II7 

.508 

•433 
.310 

.383 

6 .22 

24.72 
11 .81 

36.53 

835-95 

121 .21 

85.40 

45-01 

.4818 

.398 

42-75 

1,832.69 

1 

269 .28 

| 85.31 

I  .  1277 

.418 

1 

100. 



ioo  Alkaloids  in  Belladonna  Plant.       { Al Q^/r™r- 


Table  I. — Continued. 


Analyses  of  Four  Typical  Third-year  Belladonna  Plants. 


Weight  (grams) 

Alkaloids 

Plant  and  part 

Green 

Dry 

Moist- 

per 
cent. 

Per 
cent,  of 
entire 
plant 

Grams 

Per 
cent. 

Percentage 
of  quantity 

of  alka- 
loids in  the 
plant 

Plant  No.  2. 

Flowers 

26.67 

in- 55 

4-55 
16.63 

82 

85.O8 

2  . 04 
7-50 

.0126 

•277 

I  .21 

Flowering  tops  

.1280 

.770 

12-33 

Leaves* 
Small 

21 .00 

2-95 

27.23 
2.32 

86.00 

I  12 

12  . 20 
I  .04 

.Ol8l 

.613 

•571 

.839 

1.72 

I4.96 
I.87 

Large : 

Without  petioles . 
Petioles 

183 .00 
21 .65 

85-14 

89.30 

-I555 
.OI94 

ii/iiLire  icirgt 
leaves  

214.65 

29.55 

86.10 

I3.24 

•1749 

•592 

16.85 

Total  

235-65 

32.50 

86 .08 

I4.64 

.1930 

•597 

18.57 

Stems: 

Small  

141.70 

1 20  90 
82.30 
93.00 

18.48 

O  "2/1 

y  -o4 
9-5o 
25.07 

86.93 

92.27 
88.45 
73.00 

8.28 

.1417 

•OI45 
.0326 

.767 

IT? 

•153 
.130 

I3-63 

1-345 
3-14 

Large : 

Pith  

4.18 

Bark  

4.17 

11-23 

Wood  

Entire  large 
stems 

296 .20 

43 .91 

85.20 

19.67 

.08l8 

.186 

7.88 

Total  

437-90 

62.39 

85.80 

27-95 

■2235 

-358 

21.51 

Roots: 

Small  

105.50 

364-30 
266.70 

16.47 

53-71 
36.93 

84.40 

85.32 
86.07 

7-38 

24.07 
16.59 

•0974 

.2572 
.1274 

•592 

•479 
•345 

9-36 

24-75 
12 .27 

Large : 

Wood  

Bark  

Entire  large 

roots  

630.00 

90.64 

85-61 

40.61 

•3846 

-•424 

37.02 

Total  

735-50 

107 .11 

85-44 

52.52 

.4820 

•450 

46.38 

Entire  plant  

1.538.27 

223 . 18 

85-49 

I .0391 

.466 

Am.  Jour.  Pliarm.  > 
March,  1914.  / 


Alkaloids  in  Belladonna  Plant. 


IOI 


Table  I. — Continued. 
Analyses  of  Four  Typical  Third-year  Belladonna  Plants. 


Plant  and  part 


Plant  No.  3- 

Flowers  

Flowering  tops. . 


Leaves : 

Small  

Large: 

Without  petioles 
Petioles. .  .  


Entire  large 
leaves  


Total. 


Stems : 
Small. . . 
Large : 

Pith.. 

Bark. 

Wood 


Weight  (grams) 


Green 


Dry 


Entire  large 
stems  


Total. 


Roots : 

Small. . . 

Large : 
Wood 
Bark. 


29-75 
[04 .00 


5-26 
6.29 


28.00  4.57 

186.83  28.36 
18 .67      1  .  69 


205.50  30.05 


233-50 


34.62 


125.80 

119.30 
84.60 
98.50 


302.40 


428  .20 


212 .80 


449.90 
216 . 10 


17-49 

7.24 
7.98 
26.86 


42  .08 


59-57 


36.33 

70.54 
36.40 


Entire  large! 

roots   666 . 00  I  106 . 94 


Total   878.80 


Entire  plant  1,674.25 


143-27 


259.01 


Moist- 
ure 
per 

cent. 


82.30 
84.32 


83.70 

84.88 
90.99 


85.4O 


85.IO 


86.08 

93-49 
9035  • 
72.70 


Per^ 
cent,  of 
entire 
plant 


2.03 
6 .29 


1  -77 

10.95 
•65 


11 .60 


13.29 


6-75 

2.80 
3.08 
10.37 


86. 13  j  16  .24 


86.10  22.99 


82.97  I  14.03 
84.30  27.23 


83.20 


83-93 


83.70 


84-53 


1405 


41.29 


55-31 


Alkaloids 


Grams 


OI9I 
1379 


Per 
cent. 


366 
•847 


.0305  .669 


.1273 
OO59 


449 
354 


1332  -443 


1637  .472 


.0222 
0113 
.0306 


.0641 


1533 


2365 

3900 
1114 


5014 


7379 


21 19 


.510 

•307 
.142 
.114 


152 


257 


.651 

•553 
•  306 


.469 


515 


,468 


Percentage 
of  quantity 

of  alka- 
loids in  the 
plant 


102 


Alkaloids  in  Belladonna  Plant. 


Am.  Jour.  Pharm. 
March.  1914. 


Table  I. — Continued. 
Analyses  of  Four  Typical  Third-year  Belladonna  Plants. 


Weight  (grams) 

Alkaloids 

Plant  and  part 

Green 

Dry 

Moist- 
ure 
per 

cent. 

Per 
cent,  of 
entire 
plant 

Grams 

Per 
cent. 

Percentage 
of  quantity 

of  alka- 
loids in  the 
plant 

Plant  No.  4 
Flowers  

41  .60 
91  .OO 

8  .00 

80.60 

2.83 

5-79 

•0361 
.  1607 

•452 
.982 

3-oo 
I3-36 

Flowering  tops  

I6.37 

82  .OO 

Leaves : 

Small  

28.60 

5  00 

8l  .40 

83.60 
91.30 

1  77 

10.79 
•57 

•0378 

.  1026 
.OO81 

•757 

•337 
.502 

3-14 

8-53 
.68 

Large : 

Without  petioles . 
Petioles  

I85.50 
18  .60 

30.48 
1 .62 

Entire  large 
leaves  

204. 10 

32.10 

84.24 

1136 

.1107 

■345 

9.21 

Total  

23O.9O 

37.10 

83-75 

13-13 

•1485 

.400 

12-35 

Stems: 

195.60 

140.20 
118 .00 

22.50 

10.37 
12  .31 

88.50 

92  .60 
89.58 

73-30 

7.96 

3-67 
4  63 
13-55 

•1597 

•0431 
.OI36 
.0486 

.710 

.416 
.111 

13.28 

3-59 
1  13 
4  03 

Large : 

Pith  

Bark  

Wood  

138.30 

38.29 

.  127 

Entire  large 
stems 

396.50 

60.97 

84.  6s 

21  s8 

•1053 

•173 

8-75 

Total  

592.10 

83-47 

85-95 

29-54 

.2650 

.318 

22  .03 

Roots: 

Small  

196.20 

41530 
229.30 

35  65 

63.62 
38.34 

81 .80 

12  .62 

•I750 

•3047 
.1127 

.491 

•479 
.294 

14-55 

25-33 
9-38 

Large : 

Wood  

84-75 
83" -30 

22.52 
13-57 

Bark  

Entire  large 
roots  

644 . 60 

101 .96 

84.20 

36.08 

.4174 

•409 

34-71 

Total  

840.80 

137.61 

83.61 

48.70 

•5924 

•430 

49.26 

Entire  plant  

1,796 .40 

282.55 

84.27 

I .2027 

•425 

A\aJrXiP9i4rm'l       Alkaloids  in  Belladonna  Plant.  103 


Table  II. 

Comparison  of  Percentage  of  Alkaloids  in  Different  Parts  of  Plants. 


Alkaloids  (per  cent.) 


Part  of  plant 

Average 

Fraction 
of  aver- 

Plant 

Plant 

Plant 

Plant 

age  total 

No.  1 

No.  2 

No.  3 

No.  4 

of  4 
plants 

alkaloids 
in 

4  plcints 

Flowers  

0.445 

O.277 

O.366 

O.452 

0.385 

2 .03 

Flowering  tops  

.862 

.770 

.847 

.982 

•865 

1533 

T 

.Leaves '. 

.079 

.013 

.  009 

*7  C  *7 

•757 

.079 

3  00 

Large : 

•37° 

At  t 
.  07  I 

•449 

•337 

•434 

IO  .  90 

Petioles  

•381 

.839 

•354 

.502 

.769 

■93 

Entire  large  leaves  

•378 

•592 

•443 

•345 

•439 

11.94 

Total   

•432 

•597 

.472 

.400 

•475 

14-95 

otems: 

Qmo1 1 

.441 

.707 

.510 

.710 

.  007 

10 . 4° 

Large : 

•337 

•372 

•3°7 

.410 

•35° 

2  -97 

Bark  

.128 

•153 

.142 

.111 

•134 

1. 17 

Wood  

.105 

.130 

.114 

.  127 

.119 

3i3 

Entire  large  stems  

.156 

.186 

•152 

•173 

.167 

7.27 

Total  

•237 

•358 

•257 

.318 

.292 

17  .62 

Roots : 

Small  

.508 

•592 

.651 

.491 

.561 

12.63 

Large : 

Wood.  

•433 

•479 

•553 

■479 

.486 

26.86 

Bark  

.310 

•345 

.306 

.294 

•314 

10.58 

Entire  large  roots  

•383 

•424 

.469 

.409 

.421 

37-44 

Total  

•398 

•450 

•5i5 

•430 

•448 

50.07 

Entire  plant  

.418 

.466 

.468 

•425 

•444 

ward  detached  and  kept  separate.  The  berries  were  allowed  to  dry 
slowly  in  the  air  until  the  seeds  and  husks  could  be  separated.  The 
young  sprouts,  which  were  found  mainly  along  the  lower  portions 
of  the  large  stems,  were  from  2  to  4  inches  long  and  consisted  of 
tender  growth  of  stem  and  leaves.  Since  these  were  first-year  plants 
all  the  stems  were  rather  small  and  none  were  large  enough  to  be 


104  Alkaloids  in  Belladonna  Plant.  (\JSr,Jir 


Table  III. 

Analyses  of  Six  Typical  First-year  Belladonna  Plants. 


Plant  and  part 


Weight  (grams) 


Green 


Dry 


Moist- 
ure per 
cent. 


Per 
cent,  of 
entire 
plant 


Alkaloids 


Grams 


Per 
cent. 


Percent- 
age of 
total 
quantity 
in  the 
plant 


Plant  No.  i 

Leaves  

Small  

Large  


Young  sprouts. 


Fruit  

Calyx .  .  . 
Berries. . 

Seeds. 

Husks 


Stems.  . 
Small . 
Large . 


Roots  

Entire  plant. 


Plant  No.  2 


Leaves. . 
Small. 
Large . 


Young  sprouts. 


Fruit  

Calyx .  .  , 
Berries .  . 

Seeds. 

Husks 


Stems .  . 
Small. 
Large . 


Roots  

Entire  plant. 


134.00 
78.35 
55-65 

58.20 

350.40 
72.65 

277-75 


352.8o 
181.30 
171.50 

215.80 


27.56 

15-94 
11 .62 

8.50 

67-35 
9-95 
57-40 
44-59 
12.81 

76.68 
40.72 
35 -96 

47-17 


.20 


83.40 
4i -65 
41-75 

59 -5o 

245.70 
60.55 
185-15 


225 .26 


18.38 
9.09 
9.29 


361.15 
198 .00 

163.15 
167-90 
897-65 


54 

8 

45 
33 
12 

66 
35 
30 

J6 

182 


79 


12.23 
7.07 
5-i6 

3-77 

29.90 
4.42 
25-50 
19.86 
5.64 

34  05 
18.20 

15-93 
20.94 


70 


77 

9 

10 

■05 

78 

3 

4 

97 

77 

6 

5 

08 

83 

2 

3 

60 

78 

•5 

29 

78 

79 

.8 

4 

58 

75 

•3 

25 

20 

18 

55 

6 

65 

81 

3 

36 

50 

82 

1 

19 

60 

81 

0 

16 

90 

78 

1 

20 

07 

79-7 


1463 
0906 

0557 

0680 

1816 
0084 
1732 
1536 
0196 

0752 
0493 
0259 

2040 
6751 


•ii37 
•0594 
•0543 

.0629 

.  i960 
.0126 

.1834 
.1618 
.0216 

.0788 
.0566 
.0222 

•1793 
.6307 


53i 

569 
479 

799 

269 
085 
302 

344 
153 

098 
121 
072 

432 


21 .67 
13-42 
8.25 

10.07 

26.90 
1.24 
25-66 
22.75 
2  .91 

11 . 14 

7 -30 
3-84 

30.22 


299 


619 

654 
586 

953 

361 
152 
399 
479 
178 

118 
158 
072 

488 

346 


18 

•03 

9 

.42 

8 

.61 

9 

•98 

3i 

.08 

1 

•49 

29 

09 

25 

65 

3 

43 

12 

49 

8 

97 

3 

52 

28 

42 

Am.  Jour.  Pharm. 

March,  1914. 


Alkaloids  in  Belladonna  Plant. 


105 


Table  III. — Continued. 
Analyses  of  Six  Typical  First-year  Belladonna  Plants. 




Weight 

(grams) 

Alkaloids 

* 

Plant  and  part 

Mc 
ure 

)ist- 
per 

Per 
cent,  of 
entire 

Percent- 
age of 

Green 

Dry 

cent. 

plant 

Grams 

Per 
cent. 

total 
quantity 

in 

the 

plant 

Plant  No.  3 

Leaves  

107 

57 

25 

•44 

76 

40 

II 

.28 

•1305 

514 

20 

.06 

Small  

70 

40 

16 

■56 

76 

40 

7 

•33 

.0907 

•548 

13 

•94 

Large  

37 

17 

Q 
O 

.  CO 

76 

.  00 

3 

•95 

.0398 

•448 

6 

.  12 

46 

95 

8 

.04 

82 

90 

3 

56 

.0708 

■877 

10 

•87 

Fruit  

337 

40 

66 

83 

80 

IO 

29 

63 

.2014 

.302 

30 

93 

77 

4o 

1 0 

79 

86 

OO 

4 

71 

.0091 

.085 

I 

•39 

Rpi*np<; 

259 

95 

56 

.  I  I 

78 

30 

24 

90 

.1923 

•343 

29 

54 

Seeds  

A  A 

44 

t  n 
A9 

6/1 
D4 

•1733 

•391 

26 

61 

Husks  

1 1 

.86 

5 

26 

.OI90 

.  160 

2 

92 

363 

50 

77 

03 

79 

OO 

34 

15 

.0564 

•073 

8 

66 

Small  

154 

10 

31 

93 

78 

OO 

14 

15 

.  0298 

•°93 

4 

58 

Large  

209 

40 

45 

.  10 

78 

50 

20 

OO 

.0266 

•059 

4 

08 

197 

15 

48 

23 

75 

5° 

21 

38 

.  1920 

29 

48 

Entire  plant  

1,052 

57 

225 

57 

78 

60 

.6511 

.288 

Plant  No.  4 

Leaves  

142 

30 

27 

59 

80. 

70 

10 

•45 

.2038 

•736 

20 

37 

•vmpll 

68 

65 

13 

13 

81 

00 

4 

95 

nr>  t  ft 
.  09  I  0 

.  090 

9 

17 

73 

65 

14 

46 

80 

40 

5 

50 

.II20 

•772 

11 

20 

Young  sprouts  

5i 

92 

8 

21 

84 

20 

3 

12 

.O849 

I  .032 

8 

49 

Fruit  

398 

80 

75 

34 

81 

05 

28 

56 

.2810 

•373 

28 

09 

Calyx  

109 

45 

13 

90 

87 

10 

5 

28 

.0294 

.211 

2 

94 

Berries 

289 

35 

61 

•44 

78 

80 

23 

28 

.2516 

.409 

25 

15 

Seeds  

49 

20 

18 

66 

.2170 

.441 

21 

69 

Husks  

12 

24 

4 

62 

.O346 

■283 

3 

46 

Stems  

400 

05 

82 

63 

79 

20 

3i 

32 

.1156 

.  140 

1 1 

55 

Small  

183 

10 

36 

93 

78 

60 

14 

00 

.0661 

.179 

6 

60 

Large  

216 

95 

45 

70 

78 

90 

17 

32 

•0495 

.108 

4- 

95 

Roots  

238 

35 

70 

00 

70 

90 

26 

55 

•3I50 

•450 

31 

50 

Entire  plant  

1,231 

77 

263 

77 

78 

30 

I .0003 

•379 

io6 


Alkaloids  in  Belladonna  Plant. 


f  Am. 

1  i 


Jour.  Pliarm. 
March,  1914. 


Table  III. — Continued. 
Analyses  of  Six  Typical  First-year  Belladonna  Plants. 


Plant  and  part 


Weight  (grams) 


Green 


Dry 


Moist- 
ure per 


Per 
cent,  of 
entire 
plant 


Alkaloids 


Grams 


Per 
cent. 


Percent- 
age of 
total 

quantity 
in  the 
plant 


Plant  No.  S 


Leaves. . 
Small. 
Large. 


Young  sprouts. 


Fruit  

Calyx .  .  . 
Berries .  . 

Seeds. 

Husks 


Stems.  . 
Small. 
Large. 


Roots  

Entire  plant. 


Plant  No.  6 


Leaves. . 
Small. 
Large . 


Young  sprouts. 


Fruit  

Calyx .  .  . 
Berries .  . 

Seeds . 

Husks 


Stems .  . 

Small. 

Large . 
Roots .  . 


Entire  plant. 


113-75 
60.05 
53-7o 

51-95 

295.60 
75.06 
220.60 


331-75 
192.05 
139.70 


23-41 
12.51 
10.90 

7-52 

58.72 
9.69 
49  03 
37- 80 
11 .14 

62.13 
35  30 
26.83 


126.50  31.90 


919.55  183.68  I  81 


107.65 
57-40 
50.25 

37-55 

335-85 
80.15 
255-70 


380.70 
244.00 
136.70 
221 .50 


1,083.25 


80 


73 


50 


98 


20.72  80.70 
10.97  I  80.89 
9-75  j  80.59 

6.21  83.25 


61 .29 
9 -5o 
51-79 
37-28 

14-51 


81.50 
88.10 
79.70 


70.67  81 .40 
43.32  82.00 
27-35  79-90 
47-54  I  78.30 


12  .69 
6.80 
5-89 

4. 10 

31-99 
5-27 
26.72 
20.65 
6.07 

33-84 
19 .22 
14.62 

17-38 


206.43  80.94 


10.04 
5-3i 
4-73 

3.01 

29 .69 
4.60 
25.09 
18.06 
7-03 

34-23 
21 .00 

13 .23 
23-03 


.2135 
.1113 
.  1022 

.0790 

•1957 
.0148 
.1809 
•i55o 
.0259 

.0892 
.0626 
.0266 

.1674 


7448 


1662 
0873 
0789 

0545 

.1700 
.0132 
.1568 
•1 193 
•0375 

.0874 
.0724 
.0150 
.2247 


7028 


913 

890 

938 
052 

333 
221 

370 
409 

233 

144 
177 
099 

524 


405 


803 
794 


,876 

.277 
139 
■305 
.320 

259 

.114 
.167 
•055 
•472 


340 


Am.  Jour.  Pharm. 
March,  1914. 


Alkaloids  in  Belladonna  Plant. 


107 


separated  into  bark,  wood,  and  pith.  The  roots  also  were  much 
smaller  than  in  the  older  plants  and  were  therefore  not  separated 
into  large  and  small  roots. 

In  assaying  the  seeds  it  was  necessary  first  to  extract  the  fixed 
oil  with  petroleum  ether.  The  percentage  of  alkaloids,  however,  as 
given  in  Table  III,  is  calculated  on  the  basis  of  the  whole  seeds. 

Table  IV. 

Summary  Showing  Comparison  of  Percentages  of  Alkaloids  in  Different  Parts 

of  the  Six  Plants. 


Part  of  plant 


Alkaloids  (per  cent.) 


Plant 
No.  1 


Plant 
No.  2 


Plant 
No.  3 


Plant 
No.  4 


Plant 
No.  5 


Plant  Klf^Q 

No.  6      °f  a" 
1  plants 


Fraction 
of  average 

total 
alkaloids 
in  6  plants 


Leaves  

Small  

Large  

Young  sprouts 

Fruit  

Calyx  

Berries .... 
Seeds. . . . 
Husks .  .  . 

Stems  

Small  

Large  

Roots  

Entire  plant. . 


o.53i 
569 
479 

799 

269 
085 
302 
344 
153 

098 
121 

072 

432 


0.619 

654 
586 


953 


299 


361 
152 
399 
479 
178 

118 
158 
072 


346 


0.514 
548 
448 


877 

302 
085 
343 
39i 
160 

o73 
093 
059 

397 


0.736 
698 
772 

032 

373 
211 
409 
441 

283 

140 
179 
108 

45o 


288 


0.913 
890 
938 

052 

333 
221 

370 
409 
233 

144 
177 

099 

524 


379 


405 


803 

794 
808 

876 

277 
139 
305 
320 

259  I 

114 
167 
055 

472 


340  .3430 


6860 
6922 
6718 

9315 

3192 
1488 
3572 
3973 
2110 

1 145 
1492 

0775 
4605 


22 . 10 
12.05 
10.05 

9-53 

27.84 
1 .99 

25-85 
22.25 
3.60 


11 .41 

7.65 
3-76 

29.11 


A  critical  review  of  Tables  I  to  IV  leads  to  the  conclusion  first 
of  all  that  in  a  general  way  the  distribution  of  alkaloids  in  the 
different  parts  of  belladonna  plants  is  largely  the  same  in  different 
individual  plants.  While  it  is  probably  unwise  to  draw  definite 
conclusions  from  the  limited  number  of  plants  here  analyzed,  the 
results  are  without  doubt  largely  indicative  of  what  would  be  found 
were  analyses  made  of  many  more  plants.  Gerard  2  has  found  that 
in  both  wild  and  cultivated  belladonna  plants  the  leaves,  roots,  fruit, 

2  Gerard,  A.  W.  Report  on  the  alkaloidal  value  of  cultivated  and  wild 
belladonna  plants,  Yearbook  of  Pharmacy,  1880-1881,  pp.  482-489. 


io8 


Alkaloids  in  Belladonna  Plant. 


(Am.  Jour.  Pharm. 
\    March,  1914. 


and  stems  rank  in  the  order  named  as  regards  the  percentage  of 
alkaloidal  content.  These  observations  are  in  perfect  accord  with 
the  results  here  given.  A  number  of  interesting  facts  are  emphati- 
cally brought  out.  Of  the  aerial  part  of  the  plant  all  parts  but  the 
large  woody  stems  contain  enough  alkaloids  to  make  their  utilization 
practicable.  During  the  early  summer,  belladonna  herb,  including 
leaves,  tops,  and  small  stems,  could  be  advantageously  picked  as  far 
as  medicinal  strength  is  concerned  if  the  herb  rather  than  leaves 
were  official.  The  flowering  tops  in  the  third-year  plants  easily 
rank  first  as  containing  the  greatest  percentage  of  alkaloids.  In  all 
the  first-year  plants,  the  young  sprouts  are  found  to  contain  the 
greatest  quantity  of  alkaloids,  two  of  the  six  containing  more  than 
i  per  cent.  Attention  has  been  directed  to  the  fact  that  the  flowering 
tops  and  the  young  sprouts  represent  the  youngest  and  tenderest 
growth  in  the  third-year  and  in  the  first-year  plants,  respectively. 
Since  in  the  plants  analyzed  the  greatest  concentration  of  alkaloids 
is  found  in  these  parts,  the  logical  conclusion  is  that  the  greatest 
concentration  of  alkaloids  is  to  be  found  in  the  youngest  parts  of  the 
plants.  A  further  study  of  the  tables  will  emphasize  this  fact  still 
more.  In  seven  of  the  ten  plants  the  small  leaves  are  considerably 
richer  in  alkaloids  than  the  large  leaves,  the  average  for  the  small 
leaves  being  0.687  per  cent,  and  for  the  large  ones  0.578  per  cent. 
The  small  leaves  usually  appear  on  the  plants  later  than  the  large 
ones.  In  the  case  of  the  third-year  plants,  which  were  analyzed  in 
June,  the  small  leaves  were  found  mostly  near  the  tops  of  the 
branches,  indicating  that  they  represented  younger  growth  than 
the  large  leaves.  Later  in  the  season  there  is  always  a  preponder- 
ance of  small  leaves,  very  little  growth  of  large  leaves  taking  place 
after  the  flowering  period  is  over.  Hence,  in  all  the  plants  under 
consideration,  the  small  leaves  constitute  in  a  general  way  younger 
growth  than  the  large  ones.  The  higher  percentage  of  alkaloids  in 
the  former  is,  therefore,  parallel  to  the  condition  that  exists  in  the 
flowering  tops  and  young  shoots.  Again  it  is  seen  that  the  same 
is  true  of  the  stems.  The  average  per  cent,  of  alkaloids  in  the  small 
stems  is  0.332,  and  in  the  large  stems  0.113.  The  difference  is 
especially  marked  in  the  third-year  plants.  Here  again  those  stems 
which  constitute  the  youngest  growth  are  richest  in  alkaloids.  In 
the  four  plants  where  the  large  and  small  roots  were  separated,  the 
average  alkaloidal  content  of  the  small  roots  was  0.561  per  cent.,  and 
of  the  large  roots  0.421  per  cent.    The  small  roots,  as  has  been 


Am.  Jour.  Pharm. 

March,  1914. 


Alkaloids  in  Belladonna  Plant. 


109 


stated,  consisted  mostly  of  the  young  and  tender  ends  of  the  tap 
roots.  The  relationship  is  again  evident.  In  the  four  third-year 
plants  whose  large  stems  and  roots  were  separated  into  their  various 


Fig. 


P£f?  CEMT  OF  /4l  O/DS 


PER  CEA/r  Of /tl/f/tl0/0S 

^^^^^^^^^ 
^   ^    §    ^    ^   ^   ^  ^ 


<ZDC*n/ /T<  v 


Graphic  illustration  showing  the  distribution  of  the  alkaloids  in  the  various  parts  of  the 

Belladonna  plant. 

parts,  the  average  per  cent,  of  alkaloids  is  as  follows  :  Pith  of  stems, 
.0358;  bark  of  stems,  0.134;  wood  of  stems,  0.119;  bark  of  roots, 
0.314;  wood  of  roots,  0.486.  Figure  I  shows  graphically  the  dis- 
tribution of  alkaloids  in  the  plant. 


no 


Alkaloids  in  Belladonna  Plant. 


Am.  Jour.  Pharm. 
March,  1914. 


It  has  been  quite  generally  held  that  most  of  the  alkaloids  in  the 
roots  are  found  in  the  bark.  The  National  Dispensatory  states  that 
a  good  root  contains  alkaloids  in  the  parenchymal  tissue  of  all  parts 
though  mostly  in  the  bark,  while  in  a  woody  root  it  is  almost  ex- 
clusively in  the  bark.  This  investigation  appears  to  indicate  that 
such  is  not  always  the  case.  In  all  of  the  four  three-year  old  plants 
analyzed,  the  woody  part  of  the  roots  was  richer  in  alkaloids  than 
the  bark.  In  order  to  obtain  further  data  on  this  question,  seven 
four-year  old  plants  were  dug  up  early  in  the  fall  and  the  roots 
separated  into  bark  and  wood.  Table  V  shows  the  results  of  the 
assays. 

Table  V. 

Comparison  of  Alkaloidal   Content  of  the  Bark  and  Wood  of  the  Roots  oj 
Individual  Belladonna  Plant. 


Number  of  plant 


Alkaloids  (per  cent.) 


Bark 


O.I82 
O.163 
0.262 
O.I44 
O.205 
O.238 
O.227 


Wood 


0.217 
O.177 
O.324 
O.29O 

0.347 
O.447 
O.400 


These  results  show  further  that  the  bark  is  not  always  richer  in 
alkaloids  than  the  woody  tissue. 

It  has  been  pointed  out  that  the  small  leaves  were  found  to  be 
almost  invariably  richer  than  the  large  leaves.  This  is  a  matter  of 
some  importance  in  that  it  becomes  a  factor  in  the  method  of  pick- 
ing leaves  with  regard  to  securing  those  of  greatest  medicinal  value. 
To  establish  this  fact  more  conclusively,  large  and  small  leaves  were 
picked  from  the  individual  belladonna  plants.  At  the  same  time 
leaves  were  also  picked  from  a  number  of  species  of  Datura.  Table 
VI  shows  the  relative  percentage  of  alkaloids  in  the  leaves. 

It  will  be  noticed  that  in  only  one  instance,  plant  No.  2, 
does  the  sample  of  large  leaves  show  a  greater  percentage  of  alkaloids 
than  the  smaller.  In  all  the  others  the  difference  is  greatly  in  favor 
of  the  small  leaves,  as  is  also  indicated  by  the  averages.  All  but  one 
of  the  Datura  species  indicated  the  same  condition,  thus  showing 


A\S;  iP9u.rm' }       Alkaloids  in  Belladonna  Plant.  in 

that  the  relative  concentration  of  alkaloids  in  large  and  small  leaves, 
as  found  in  belladonna,  exists  also  in  other  members  of  the  solan- 
aceous  family.  Since  the  small  leaves  are  as  a  rule  younger  than  the 
large  ones,  it  would  seem  that  the  greater  concentration  of  alkaloids 
in  the  former  is  due  to  greater  cell  activity.  It  would  be  expected 
that  there  would  be  a  general  graduation  in  the  concentration  of 
alkaloids  from  the  youngest  to  the  oldest  leaves.  To  determine  this 
point  two  rows  each  containing  about  75  plants  were  selected.  From 

Table  VI. 


Comparison  of  Alkaloidal  Content  of  Large  and  Small  Leaves  from  Individual 
Plants  of  Atropa  Belladonna  and  Various  Species  of  Datura. 


Alkaloidal 

Alkaloidal 

content  of  leaves 

content  of  leaves 

Plant  analyzed 

(per  cent.) 

Plant  analyzed 

(per  cent.) 

Large 

Small 

Large 

Small 

Atropa  bella- 

0.268 

O.418 

donna  : 

D.  fastuosa  No.  29646  

.438 

.478 

Plant  No.  1 

O.342 

O.657 

D.  gigantea  

.165 

.179 

Plant  No.  2 

•743 

.706 

D.  quercifolia  

.228 

.368 

Plant  No.  3 

.685 

.915 

D.  fastuosa  No.  29644  

•423 

•479 

Plant  No.  4 

.840 

.929 

D.  stramonium  inermis  .... 

.221 

•511 

Plant  No.  5 

.864 

.904 

D.  tatula  

.218 

.241 

Plant  No.  6 

.718 

.831 

.277 

.271 

Plant  No.  7 

•537 

•723 

D.  leichardti  

•175 

.189 

Plant  No.  8 

.960 

I  .074 

.190 

•454 

Plant  No.  9 

•775 

.924 

D.  stramonium  (red  stem) 

.176 

.381 

Plant  No.  10 

•570 

.990 

•133 

•475 

.306 

.441 

Average  . . . 

•703 

.865 

.247 

.378 

each  row  8  samples  of  leaves  were  picked,  ranging  from  the  smallest 
to  the  largest.  Each  sample  was  taken  from  the  entire  row  so  that 
leaves  from  all  the  plants  were  included.  By  this  means,  the  factor 
of  individual  plant  variation  was  eliminated  as  much  as  possible. 
The  following  table  shows  the  per  cent,  of  alkaloids  in  each  sample. 

In  row  No.  1  the  average  of  the  first  and  last  four  samples  are 
0.639  anQl  0.308  per  cent.,  respectively,  while  in  row  No.  2  the  aver- 
ages are  0.695  and  0402,  respectively.  It  is  evident  that  if  too  many 
of  the  larger  leaves  are  included  the  sample  will  assay  relatively  low 
and  will  hardly  give  a  fair  indication  of  the  value  of  the  plant.  There 
is  a  natural  tendency  to  pick  such  leaves  because  they  can  be  more 


112  Toxic  Constituent  of  Poison  Ivy.  -jAl 

Table  VII. 


Comparison  of  Alkaloidal  Content  of  Belladonna  Leaves,  Varying  in  Size  from 
the  Smallest  to  the  Largest,  each  Sample  being  a  Collective 
Picking  from  the  Entire  Row. 


Row  No.  i. 

Row  No.  2. 

Sample 

Alkaloids  (per 
cent.) 

Sample 

Alkaloids  (per 
cent.) 

i  (smallest) 

2 

3 
4 
5 

6 

7 

8  (largest) 

0.62I 
O.706 
O.664 
O.766 
O.598 
O.406 
O .  I IO 
O.  Il6 

I  (smallest) 

2 

3 

4 

5 

6 

7 

8  (largest) 

0.598 
O.700 
O.669 

0 .804 

O.605 
0.523 
0.324 
0.212 

rapidly  picked  owing  to  their  size.  It  is  economically  out  of  the 
question  to  pick  such  leaves  as  constitute  samples  1  and  2,  while 
samples  3  to  6  should  represent  the  best  leaves  available  for  all  pur- 
poses, appearance  as  well  as  strength,  and  from  both  the  medicinal 
and  commercial  standpoint. 


THE  VOLATILE  NATURE  OF  THE  TOXIC 
CONSTITUENT  OF  POISON  IVY. 

By  Charles  E.  Bessey. 

There  is  a  pretty  general  agreement  among  medical  men  that 
the  active  poisonous  principle  in  Poison  Ivy  (Rhus  radicans  L., 
Toxicodendron  radicans  (L.)  Kuntze)  is  a  non- volatile  oil,  and 
that  as  a  consequence  poisoning  without  contact  is  impossible.  Yet 
there  are  many  assertions  to  the  contrary  by  those  who  have  been 
victims  of  this  poisonous  principle.  I  have  heard  persons  assert 
that  they  had  been  poisoned  when  walking  or  driving  by  the  Poison 
Ivy.  I  have  always  maintained  a  feeling  of  considerable  doubt  in 
regard  to  such  cases,  for  it  is  obviously  difficult  to  prove  lack  of 
contact. 

However,  I  myself  once  suffered  from  a  severe  case  of  poisoning 
without  contact,  as  I  reported  a  few  years. ago  in  a  paper  entitled 
"A  Preliminary  Account  of  the  Plants  of  Nebraska  which  are 


AmMaJr°chr'  Si*™1' }     Toxic  Constituent  of  Poison  Ivy.  113 

Reputed  to  be  Poisonous,  or  are  Suspected  of  Being  So,"  and  pub- 
lished in  the  Annual  Report  of  the  Nebraska  State  Board  of  Agri- 
culture for  1901.  This  account  is  so  detailed  that  I  repeat  it  here, 
as  follows : 

"  An  assistant  brought  into  my  laboratory  a  tin  box  full  of 
plants,  among  which  were  many  flowering  specimens  of  the  Poison 
Ivy.  The  day  was  hot,  and  the  assistant  had  walked  in  the  sun  for 
a  mile  or  more,  in  bringing  in  the  plants.  Knowing  my  suscepti- 
bility to  Poison  Ivy  poisoning  he  warned  me  not  to  touch  the  tin 
box  or  its  contents.  I  therefore  told  him  to  open  the  box  while 
I  looked  on  and  selected  the  plants  which  1  wished  him  to  preserve 
for  pressing.  As  the  box  was  opened  I  leaned  over  and  looked  in, 
being  very  careful  not  to  come  into  contact  with  the  box  or  the 
plants.  As  the  assistant  took  up  plant  after  plant  I  pointed  to 
others  and  asked  him  in  regard  to  the  stations  where  he  secured 
them.  I  was  very  careful,  as  I  had  been  very  severely  poisoned 
many  times  before,  and  did  not  wish  to  have  another  experience  of 
the  discomfort.  Yet  in  a  day  or  two  I  found  myself  suffering  with 
the  usual  inflammation,  only  the  surfaces  affected  were  those  only 
which  had  been  directly  exposed  when  I  leaned  over  the  box  of 
plants.  My  face  was  inflamed  all  over,  except  where  my  beard, 
mustache,  eyebrows,  and  nose  made  projecting  protections.  Above 
these  there  were  small  areas  entirely  free  from  inflammation.  The 
under  side  of  my  eyebrows  (the  'overhang')  was  thoroughly 
poisoned,  and  so  was  the  inside  of  my  nose  (the  nostrils).  My 
right  hand  was  severly  poisoned,  but  here  again  the  distribution  of 
the  inflammation  was  peculiar,  being  confined  to  the  parts  which 
were  directed  dozvnward  as  I  pointed  at  the  various  specimens  in 
the  box.  Thus  the  proximal  and  middle  joints  of  the  second,  third 
and  fourth  fingers,  and  the  under  side  of  the  wrist  of  that  hand 
were  badly  affected,  while  the  upper  side  of  the  hand  was  not 
poisoned  at  all.  My  left  hand  was  not  poisoned,  and  I  account  for 
this  by  the  fact  that  it  was  kept  back  and  not  used  in  indicating 
plants  to  be  examined  by  the  assistant." 

I  do  not  see  how  any  one  can  escape  from  the  conclusion  that 
that  which  poisoned  me  so  severely  and  so  peculiarly  was  volatile 
enough  to  be  carried  up  (apparently  in  straight  lines)  in  the  warm 
air  which  escaped  from  the  tin  collecting  box  (vasculum)  when 
opened  in  my  study.  In  this  case  there  was  no  contact  on  my  part 
with  the  Poison  Ivy,  nor  with  any  other  plants  in  the  vasculum.  I 


ii4 


had  been  poisoned  too  often  to  be  careless  when  warned  by  my 
assistant.  I  am  not  denying  the  truth  of  Dr.  Pfaff's  conclusion  that 
there  is  a  non-volatile  poisonous  oil  in  the  Poison  Ivy.  I  am  forced 
to  conclude  that  there  is  a  volatile  poison,  also,  in  this  plant. 

The  University  of  Nebraska. 


APPLIED  PHARMACOGNOSY. 
Some  Observations  of  a  Graduate. 
By  J.  R.  Rippetoe. 

What  are  you  going  to  do  one  year  from  to-day  or  what  will 
you  be  doing?  You  don't  know,  certainly  not.  If  it  were  possible 
for  you  to  know,  wouldn't  you  prepare  to  make  that  day's  work  a 
success  ? 

Did  it  ever  occur  to  you  to  try  and  imagine  what  kind  of  a 
world  this  would  be  if  every  man  could  begin  at  his  deathbed  and 
live  life  back  to  birth  or  in  other  words  live  his  life  over  again  with 
the  advantages  of  the  experience  and  knowledge  gained  in  his 
lifetime?  Old  age  says  my  days  have  passed  but  youth  is  full  of 
ambition  and  hopes  for  the  future. 

The  laws  of  nature  give  man  only  one  life  but  the  law  of  evolu- 
tion gives  youth  all  the  advantages  of  the  experience  of  old  age. 
We,  therefore,  in  our  lifetime  take  from  the  present  and  the  past 
varying  portions  of  its  offerings. 

You  are  now  learning  the  principles  of  Pharmacy  and  soon  you 
will  be  as  fully  equipped  as  the  learned  professors  and  instructors 
in  this  college  can  teach  you  and  as  much  as  you  are  willing  to  learn. 

The  point  I  want  to  take  up  with  you  is  the  application  of  your 
knowledge.  Some  of  you  will,  no  doubt,  take  up  manufacturing 
pharmacy.  Those  of  you  who  will  take  up  retail  pharmacy  will 
find  my  remarks  equally  applicable  to  your  position. 

What  are  the  duties  of  a  pharmacist  or  a  pharmaceutical  chemist 
in  a  pharmaceutical  laboratory? 

The  first  operation  is  the  writing  of  a  working  formula.  If  an 
official  preparation  is  to  be  made  this  is  not  difficult,  but  I  have 
seen  some  men  spend  several  hours  in  trying  to  calculate  the  quan- 
tities of  each  ingredient  when  the  formula  may  be  given  to  them  for 
one  fluidounce  or  one  tablet,  as  the  case  may  be,  and  even  then 


%ar°chr;iP9irm"}  Applied  Pharmacognosy.  115 

not  have  it  correct.  A  formula  may  state  the  grains  or  minims  in 
each  fluidounce  and  for  practical  purposes  it  must  be  calculated  to 
the  proper  quantities  to  make  100  liters. 

As  many  liquids  are  bought  and  sold  by  weight  and  it  is  also 
more  practical  to  handle  them  by  weight  the  minims  must  be  con- 
verted into  grammes  and  kilos.  The  specific  gravity  of  the  liquids, 
therefore  must  also  be  considered.  Calculating  many  liquids  to 
weight  is  absolutely  necessary  for  figuring  costs. 

The  quantity  to  be  made  is  primarily  governed  by  the  demand 
but  there  is  to  be  considered  among  other  things  cost  of  raw 
material.  This  is  particularly  to  be  considered  with  crude  drugs 
which  at  times  offer  about  as  much  opportunity  for  speculation  as 
stocks  in  Wall  Street.  With  such  drugs  as  ergot,  jalap,  ipecac, 
hydrastis  and  opium  varying  in  price  from  50  cents  to  $10.00  per 
pound  and  the  price  fluctuating  with  the  season  or  crop  it  is  neces- 
sary to  keep  an  eye  on  the  market  and  your  stock  and  sales. 

The  buying  of  crude  material  and  selling  of  the  finished  products 
are  of  course  taken  care  of  by  separate  departments,  but  the  manu- 
facturing comes  in  between  and  requires  some  knowledge  of  the 
buying  and  selling.  The  buying  and  selling  departments  offer 
good  inducements  to  college  trained  men,  the  selling  in  particular 
to  men  who  are  more  inclined  to  the  commercial  side  rather  than 
the  scientific  side  of  pharmacy. 

If  a  fluidextract  or  some  drug  preparation  is  to  be  made  and 
there  is  no  stock  of  crude  drug  on  hand  the  purchase  of  drug  is 
taken  up  with  the  buying  department.  The  buying  department  asks 
for  quotations  and  samples  of  the  drug  offered,  especially  if  the 
drug  is  one  that  has  some  official  standard.  The  samples  are  care- 
fully examined  for  freedom  from  foreign  drugs  and  assayed  for 
alkaloidal  or  extractive  content. 

The  analytical  reports  are  compared  and  the  price  also  taken 
into  consideration  for  selecting  the  lot  of  drug  to  be  purchased. 
With  assayed  drugs  for  example  the  price  may  not  vary  very  much 
but  the  alkaloidal  content  may  vary  as  much  as  100  per  cent. 

Since  most  drug  preparations  are  made  by  extracting  the  drug 
with  an  alcoholic  menstruum  varying  in  strength  from  10  to  95 
per  cent,  absolute  alcohol,  and  alcohol  costs  about  $2.50  per  gallon 
by  the  barrel,  means  must  be  employed  for  carrying  out  the  opera- 
tions to  prevent  loss  in  handling,  evaporation  and  final  recovery 
from  the  exhausted  drug. 


n6 


Applied  Pharmacognosy. 


/  Am.  Jour.  Pharm. 
\     March,  1914. 


All  liquids  are  best  handled  by  allowing  them  to  flow  from  one 
vessel  to  another  by  gravity  or  by  means  of  pumps  to  produce  both 
pressure  and  vacuum  as  may  be  required. 

Ofttimes  it  is  necessary  to  carry  out  a  number  of  experiments 
to  determine  the  best  combination  of  alcohol  and  water,  and  some- 
times with  glycerin  or  acid  added,  to  extract  the  desirable  con- 
stituents. 

In  the  making  of  pills  and  tablets,  excipients  or  the  proper  liquid 
for  granulating  the  ingredients  are  to  be  considered.  This  requires 
a  knowledge  of  the  properties  of  the  ingredients.  In  making  tablets 
the  ingredients  may  be  granulated  by  adding  water,  alcohol,  ether, 
chloroform,  petroleum  benzin,  other  volatile  liquids  or  combina- 
tions of  these. 

Many  formulas  that  are  official  in  the  U.  S.  P.  or  N.  F.  are 
practical  for  small  quantities  or  immediate  use  but  for  large  quan- 
tities and  indefinite  future  use  are  not  always  satisfactory.  The 
U.  S.  P.  permits  modification  of  the  methods  providing  the  finished 
products  do  not  differ  in  their  properties.  Therefore,  even  in  the 
official  preparations,  we  have  numerous  problems  for  investigation. 
Elixir  Iron,  Quinine  and  Strychnine  Phosphates  U.  S.  P.  is  a 
splendid  example  of  the  manufacturers'  problems  and  for  that  matter 
the  retail  druggist  also.  Every  issue  of  the  various  drug  Journals 
brings  forth  some  new  suggestion  until  it  seems  every  one  must  have 
a  different  method  for  making  it. 

Elixirs  or  similar  preparations  are  very  popular  as  a  means  for 
administering  most  any  drug  and  I  might  say  whether  it  has  merits 
or  not.  They  are  often  very  troublesome  to  make.  Prior  to  the 
Food  and  Drugs  Act  and  even  now,  in  some  few  cases  everything 
seemed  to  be  sacrificed  for  elegance  in  appearance,  color,  flavor,  etc., 
and  the  ingredients  claimed  to  be  present  were  conspicuous  by  their 
abscence  excepting  in  the  very  imposing  gun-shot  formula  upon  the 
label. 

The  pharmacist  in  filling  a  prescription  can  excuse  his  or  the 
physician's  unintended  precipitating  mixtures  by  putting  on  a 
"  shake  well  "  label  but  not  so  with  the  pharmaceutical  manufacturer. 
Only  clear  non-precipitating  preparations  can  be  sent  out,  and  there 
must  not  be  any  changing  in  color  and  ofttimes  druggists  expect 
them  to  stand  storage  in  zero  temperature  and  serve  for  a  window 
display  in  a  window  subject  to  the  sun's  rays  throughout  the  day. 

We  must,  therefore,  consider  the  solubility,  stability,  incom- 


Am.  Jour.  Pharm. ) 
March,  1914.  / 


Applied  Pharmacognosy. 


117 


patibility  or  means  for  controlling  any  one  or  all  of  these  properties 
of  each  and  every  ingredient  in  the  preparation.  And  last  but  not 
least  the  color  and  flavor  must  be  pleasing  to  the  eye  and  taste. 

It  is  these  characteristics,  the  last  two  in  particular,  that  have 
built  up  the  pharmaceutical  manufacturer's  business  at  the  expense 
of  the  druggist,  and  the  physician's  ability  as  a  prescription  writer. 

You  might  think  the  manufacturer  has  his  formulas  all  highly 
perfected  and  there  is  nothing  more  to  be  done.  This  is  not  always 
the  case.  Purer  chemicals  are  produced,  solubilities  and  incom- 
patibilities may  be  changed  or  some  new  procedure  of  manipulation 
is  learned.  We  therefore  have  before  us  a  continual  line  of  sub- 
stances and  preparations  for  research. 

If  a  new  or  modified  formula  is  to  be  made  up  it  is  always  ad- 
visable to  make  up  a  small  quantity,  taking  note  of  each  step  and 
carefully  observing  just  what  reactions  take  place.  Possibly  a 
number  of  combinations  are  indicated  and  about  the  only  way  to 
prove  their  value  is  to  make  up  the  combinations  and  test  them 
out  under  all  conditions.  Each  lot  may  be  divided  into  portions 
and  one  of  each  placed  in  the  sunlight,  a  hot  closet,  an  ice  box, 
humid  atmosphere  and  a  control  under  normal  conditions. 

When  the  satisfactory  combination  is  decided  upon,  the  manipu- 
lation and  apparatus  for  handling  large  quantities  is  to  be  con- 
sidered. 

Means  for  weighing  and  measuring,  mixing,  mechanical  appa- 
ratus, kettles  for  heating,  filtering,  storage,  bottling  or  filling  pack- 
ages are  problems  always  to  be  solved.  Since  the  difference  between 
raw  material  and  finished  product  is  labor,  practical  apparatus  and 
economical  manipulation  stand  between  profit  and  loss. 

After  the  preparation  is  finished  and  ofttimes  during  the  opera- 
tion various  assays  are  made  to  check  up  the  process,  also  for 
standardized  preparations  which  are  usually  made  overstrength 
and  adjusted  by  assay.  Fluidextracts,  elixirs,  syrups,  etc.,  are 
assayed  for  alcohol,  alkaloids,  extractive,  specific  gravity ;  tablets 
and  pills  for  weight  and  ingredients  ;  ointments  for  grittiness,  also 
powders ;  emulsions  for  efficiency  of  emulsification,  etc. 

As  the  majority  of  men  seeking  employment  in  a  pharmaceutical 
laboratory  prefer  to  get  into  the  analytical  department  I  want  to 
say  a  few  words  about  the  work.  I  don't  mean  to  be  sarcastic  or 
to  ridicule  any  one,  but  I  want  to  point  out  to  you  the  problems  by 
telling  you  how  they  should  not  be  done. 


ii8  Applied  Pharmacognosy.  [ 

I  trust  that  every  student  in  this  audience  will  receive  his  diploma 
at  the  appointed  time.  We  occasionally  meet  students  who  go  to 
college  for  a  diploma  and  not  an  education.  I  recall  a  classmate 
of  mine  who  took  his  freshmen  year  in  this  college  and  did  not  show 
up  again  until  the  senior  year.  He  stated  that  he  had  spent  his 
junior  year  in  another  college  taking  a  Ph.G.  degree  and  by  re- 
turning here  for  the  senior  year  would  receive  another  degree.  Pos- 
sibly, a  man  with  as  much  ability  to  corner  the  market  in  degrees 
will  succeed  in  his  own  way. 

Many  graduates  seem  to  think  that  with  commencement  study 
ends.  If  that  is  the  way  you  feel  about  it  you  want  to  change  your 
future  plans  at  once. 

I  recall  a  former  analytical  assistant  of  mine  who  considered 
attending  pharmaceutical  and  chemical  association  meetings  and 
the  reading  of  journals  a  waste  of  time.  His  work  was  typical  of 
his  knowledge. 

Upon  asking  him  why  he  ignited  a  tablet,  which  had  been  given 
him  to  test  for  morphine,  he  replied  that  he  was  going  to  test  the 
ash  for  the  morphine.  When  told  he  was  not  getting  the  results 
he  should  in  making  a  preparation  he  stated  that  he  had  not  studied 
it  in  college.  If  I  felt  that  way  about  my  work  I  would  have  to  stay 
in  college  the  balance  of  my  life. 

One  of  the  most  essential  things  in  your  work  is  several  good 
drug  journals  and  if  interested  in  chemistry  a  journal  on  chemistry 
also.  They  are  absolutely  necessary  if  you  want  to  keep  abreast  of 
the  times.  You  may  have  plenty  of  ideas  of  your  own  to  keep  you 
busy  but  the  other  fellows  have  some  too  and  unless  you  take  ad- 
vantage of  the  new  discoveries  that  are  being  announced  every  day 
it  won't  be  many  years  until  you  will  find  yourself  surrounded  by 
cobwebs  of  a  vintage  of  the  year  you  graduated. 

Some  men  will  say  I  haven't  the  time  to"  read  journals  or  I 
haven't  the  money.  Membership  in  the  American  Pharmaceutical 
Association  is  $5.00  a  year  and  the  best  drug  Journal  can  be  had  for 
$r.5o  per  year.  Two  cents  a  day  will  pay  for  them.  As  to  time, 
thirty  minutes  a  day  would  more  than  suffice  to  read  every  line  in 
the  two  publications  and  at  the  same  time  do  a  little  thinking,  also 
to  see  that  each  number  is  put  away  in  some  systematic  manner  for 
future  reference. 

I  recall  two  men  who  have  been  my  assistants  by  the  way  they 
did  analytical  work  with  pencil  and  paper  rather  than  with  the  bal- 


1914™'}  Applied  Pharmacognosy.  119 

ance  and  burette.  Why  all  this  detail  anyhow  ?  The  U.  S1.  P.  contains 
many  tests  and  assays  for  determining  the  purity  of  the  official 
preparations,  but  these  men  seemed  to  think  that  since  the  majority 
of  samples  received  for  testing  were  all  right,  they  could  make  a 
guess  at  the  purity,  figure  the  results  backward  and  get  out  of  doing 
the  tedious  work  which  for  them  required  too  much  patience.  Quite 
naturally  their  methods  were  soon  detected  and  fortunately  no  harm 
came  of  it  outside  of  the  laboratory.  But  we  cannot  say  as  much  for 
them.  They  were  destroying  their  self-respect,  ambition  and  their 
opportunities  for  success. 

These  are  the  kind  of  men  you  are  most  likely  to  hear  saying 
in  after  years,  "  I  never  had  a  chance." 

Confidence  in  your  ability  is  essential  but  some  men  are  so  con- 
ceited about  it  that  they  become  blinded  to  their  errors.  It  might 
be  all  right  to  have  the  other  man  believe  you  thoroughly  capable 
but  you  should  not  let  that  feeling  prejudice  the  analysis  of  your 
own  mind  and  knowledge.  When  the  other  man  finds  you  out  his 
confidence  in  you  will  be  very  much  weakened. 

This  failing  may  be  attributed  to  several  reasons.  It  is  usually 
due  to  narrow-mindedness,  snobbishness,  false  pride,  all  of  which  are 
due  to  ignorance.  It  indicates  the  failure  to  have  grasped  the 
primary  objects  in  attending  college,  namely,  to  obtain  a  knowledge 
of  the  basic  principles  of  the  subject  and  the  failure  to  continue  the 
line  of  study  after  leaving  college.  Give  the  text-books  you  are 
using  here  the  most  prominent  place  in  your  future  undertakings 
and  add  to  them  from  time  to  time  when  some  good  book  useful, 
particularly  for  reference,  is  called  to  your  attention.  These  books 
with  the  Journals  mentioned  before  are  the  backbone  of  your 
success.  Speaking  of  mistakes,  I  recall  a  former  assistant  who  was 
very  confident  of  his  ability  and  would  have  you  believe  that  his 
knowledge  was  complete,  he  could  make  any  kind  of  an  analysis,  he 
could  not  be  in  error.  He  said  he  was  not  in  error  when  he  obtained 
a  result  much  too  low  in  assaying  a  sample  of  ipecac  but  the  method 
was  faulty.  He  tried  it  again  several  times,  always  obtaining  a 
different  result  which  was  much  too  low.  After  his  last  failure  I 
picked  up  a  beaker  which  he  had  used  for  evaporating  the  etherial 
solution  of  the  alkaloids  and  subsequent  titration  and  called  his 
attention  to  the  resinous  mass  of  alkaloids  coating  the  side  of  the 
beaker  which  he  had  failed  to  dissolve  in  the  volumetric  acid  solu- 
tion.  Another  man  required  over  one  day  to  find  out  that  a  sample 


120 


The  Assay  of  Zinc  Stearate. 


{Am.  Jour.  Pharm. 
March,  1914. 


labelled  sodium  thiosulphate  was  not  what  it  was  labelled,  and  then 
he  spent  several  hours  more  in  finding  out  that  it  was  potassium 
nitrate. 

I  could  tell  you  of  many  more  such  incidents.  It  is  almost 
unbelievable  that  men  who  have  been  graduated  by  leading  institu- 
tions of  learning  can  be  so  helpless.  The  problems  of  the  com- 
petition of  life  bring  us  to  our  senses  and  then  we  realize  the  op- 
portunities that  have  been  thrown  away. 

Coming  back  to  my  opening  question,  "  What  are  you  going  to 
do  one  year  from  to-day?"  If  you  take  advantage  of  the  oppor- 
tunities before  you  during  the  year,  you  will  be  well  equipped  to 
consider  with  intelligence  any  problem  that  may  be  presented  to  you 
one  year  from  to-day. 


THE  ASSAY  OF  ZINC  STEARATE. 
By  Hans  Gesell. 

In  the  last  few  years  the  use  of  Zinc  Stearate  as  an  antiseptic  ■ 
and  astringent  has  been  constantly  increasing;  it  is  rather  difficult, 
however,  to  obtain  this  salt  free  from  impurities,  namely  alkalies, 
alkali  earths,  chlorides,  and  oleates.  The  tests  in  the  Pharmacopoeia 
do  not  give  concordant  results,  so  there  is  no  question  of  the  de- 
sirability of  assay  methods  which  will  be  accurate,  yet  simply  and 
rapidly  carried  out  by  analysts.  An  excess  of  Zinc  Oxide  and  Zinc 
Oleate  seem  to  be  the  most  frequent  admixtures. 

The  usual  analytic  method  by  which  the  stearic  acid  is  liberated 
by  means  of  hydrochloric  acid  and  floats  on  the  surface  of  the  hot 
liquid,  also  holds  good  for  any  Zinc  Oleate  present,  and  if  not  in 
excess,  will  even  congeal  with  the  stearic  acid  on  cooling.  This 
difficulty  can  easily  be  overcome  as  follows : 

Take  I  gm.  of  Zinc  Stearate  and  heat  with  10  c.c.  of  distilled 
water  and  i  c.c.  of  hydrochloric  acid.  The  Stearic  and  oleic  acid 
will  be  liberated  and  float  as  an  oily  layer.  Let  cool  and  this  layer 
will  solidify.  Pour  off  acid  liquid  and  wash  the  cake  several  times 
with  water.  Let  dry.  Determine  the  melting  point.  Pure  Sfearic 
acid  melts  at  690,  but  as  the  Stearic  acid  of  the  market  usually  con- 
tains Palmitic  acid,  the  melting  point  is  usually  55— 560.  Therefore, 
the  melting  point  of  this  cake  should  not  be  below  55 0 — a  lower 
melting  point  would  surely  point  to  the  presence  of  oleic  acid. 


Am.  Jour.  Pharm.  ) 
March,  1914.  J 


Sale  of  Bichloride  Tablets. 


121 


The  residue  after  incineration  which  is  chiefly  Zinc  Oxide  should 
be  about  13  per  cent.  It  is  certain  Zinc  Oxide  does  not  harm  in  a 
preparation  of  this  nature,  yet  it  is  advisable  to  determine  if  it  is 
really  Zinc  Oxide.   It  is  best  done  in  the  following  manner : 

Take  5  gm.  of  Zinc  Stearate,  add  10  c.c.  of  V2  N  HC1  and  warm 
gently  until  all  the  Zinc  Stearate  is  decomposed.  Then  with  y2  N 
NaOH  (Dimethyl  Orange)  titrate  back  the  hydrochloric  acid  not 
used.  Subtract  this  from  the  10  c.c.  taken,  multiply  it  by  the  factor 
of  Zinc  Oxide,  divide  by  the  weight  of  Zinc  Stearate  taken,  this  will 
give  the  amount  of  Zinc  Oxide  in  the  compound.  The  Stearic  acid 
could  also  be  liberated  and  determined  here,  by  simply  separating 
the  two  liquids  (warm),  rejecting  the  aqueous  portion,  using  phenol- 
phthalein  as  indicator  and  titrating  with  y2  N  NaOH. 

In  a  series  of  5  experiments  the  following  results  were  obtained : 


Melting  point 

Residue  after  incineration 

Zinc  found 

49—50° 
55-56° 
55—56° 

54—  55° 

55-  56° 

19.3  per  cent. 
13.6  per  cent. 
13  .8  per  cent. 
14 .6  per  cent. 
18  .7  per  cent. 

15  . 1  per  cent. 

10 .8  per  cent. 

10.9  per  cent. 
1 1  . 2  per  cent. 
14.8  per  cent. 

THE  SALE  OF  BICHLORIDE  TABLETS.1 

♦  A  Discussion  of  the  Need  for  Restriction  of  the  Sale  and 
Distribution  of  Bichloride  of  Mercury  Tablets. 

By  Martin  I.  Wilbert, 

Technical  Assistant,  Hygienic  Laboratory,  United  States  Public  Health  Service. 

Some  months  since  an  alleged  case  of  accidental  poisoning  by 
corrosive  mercuric  chloride,  in  Macon,  Ga.,  was  "  featured "  in 
practically  all  of  the  daily  papers  of  the  United  States  in  such  a  way 
as  to  lead  the  unknowing  to  infer  that  poisoning  by  this  substance 
guaranteed  not  alone  a  sure  but  also  a  painless  death. 

The  notoriety  given  this  case  was  followed  by  an  apparently  un- 
usual number  of  corrosive  sublimate  fatalities,  reported  from  the 

1  Reprint  from  the  Public  Health  Reports,  vol.  xxviii,  No.  46,  Nov.  14, 
1913. 


122 


Sale  of  Bichloride  Tablets. 


(  Am.  Jour.  Pharm. 
\     March,  1914. 


various  parts  of  the  United  States;  and  the  publicity  given  to  the 
harrowing  details  in  connection  with  several  of  the  cases  was  in 
turn  followed  by  agitation  for  legislation  on  the  part  of  some  of 
the  firm  believers  in  the  power  of  statute  law  to  right  all  wrongs 
and  to  correct  or,  better,  to  prevent  all  possible  abuses. 

Bills  designed  to  restrict  fatalities  from  the  accidental  taking  of 
tablets  containing  corrosive  mercuric  chloride  have  been  introduced 
in  several  of  the  State  legislatures.  In  Pennsylvania,  an  act  pro- 
hibiting the  sale  of  bichloride  of  mercury  at  retail  except  upon  the 
prescription  of  a  registered  physician  was  adopted  by  both  houses  of 
the  legislature,  but  vetoed  by  the  governor  for  the  reason  that  "  the 
public  is  amply  protected  regarding  this  drug  by  the  restrictions  put 
upon  the  sale  of  other  poisons.  Besides,  I  am  informed  that  it  is  a 
household  commodity."  As  the  agitation  for  special  legislation  to 
restrict  or  at  least  regulate  the  sale  of  tablets  of  corrosive  mercuric 
chloride  is  destined  to  be  revived  by  the  supposedly  accidental  poi- 
soning of  a  Brooklyn  business  man  and  to  continue  for  some  time  to 
come,  it  may  be  of  advantage  to  review  briefly  the  several  factors 
involved,  the  abuses  really  existing,  the  propositions  that  have  been 
made  to  correct  them,  the  safeguards  already  established,  and  the 
possible  ways  and  means  of  bringing  about  desirable  changes. 

While  it  will  generally  be  admitted  to  be  impracticable  to  prevent 
suicide  or  violent  death  by  law  or  regulation,  it  is  nevertheless  well 
recognized  that  despondent  and  melancholy  humanity  is  ever  ready 
to  seize  upon  any  suggestions  that  offer  sure,  speedy,  and  painless 
death,  so  that  every  report  of  death,  accompanied  by  the  details  of 
the  means  and  methods  producing  it  can  be  counted  on  as  an  incen- 
tive for  other  deaths  brought  about  in  much  the  same  way. 

It  is  perhaps  unfortunate  that,  for  the  rational  study  of  the  prob- 
lem before  us,  no  definite  and  satisfactory  information  is  available 
as  to  the  conditions  actually  existing  in  our  own  country.  Our 
mortality  statistics  give  only  general  death  rates  and  standardized 
death  rates,  without  furnishing  any,  even  approximate,  information 
regarding  the  nature  of  the  poison  used  or  taken  in  cases  of  reported 
fatalities.  There  is,  however,  available  in  the  report  of  the  registrar- 
general  of  births,  deaths,  and  marriages  for  England  and  Wales, 
a  detailed  account  of  the  nature  and  kind  of  substances  used,  both 
in  suicides  and  in  accidental  deaths,  and  a  careful  study  of  the  tables 
herewith  presented  will  suffice  to  demonstrate  the  impracticability 
of  legislating  specifically  for  any  one  poison.    The  tables  also  at 


Am.  Jour.  Pharm. ) 
March,  1914.  j 


Sale  of  Bichloride  Tablets. 


123 


least  suggest  the  fact  that  there  is  probably  little  or  no  cause  for 
undue  excitement  in  regard  to  the  possible  number  of  deaths  from 
the  internal  use  of  corrosive  mercuric  chloride  and  that,  granting 
that  conditions  in  England  and  this  country  are  much  the  same, 
corrosive  mercuric  chloride  plays  but  a  minor  part  in  the  number  of 
deaths  due  to  ingested  poison.  This  fact  is  further  emphasized  when 
we  realize  the  very  widespread  use  and,  incidentally  at  least,  abuse, 
of  tablets  of  corrosive  mercuric  chloride  and  the  comparatively  few 
fatalities  on  record  resulting  from  its  internal  administration.  Even 
a  careful  search  of  the  literature  since  the  report  of  the  case  at 
Macon,  Ga.,  shows  that  possibly  15,  certainly  not  over  20,  deaths 
have  been  reported  from  the  ingestion  of  corrosive  mercuric  chloride 
since  that  time.    When  we  remember  that  in  the  registration  area 


Suicides  and  accidental  deaths  from  scheduled  poisons  reported  by  the 
registrar-general  of  births,  deaths,  and  marriages  for  England 
and  Wales  for  the  year  1911. 


Poison. 

Suicides. 

Accidental  deaths. 

Total 
deaths. 

Male. 

Fe- 
male. 

Total. 

Male. 

Fe- 
male. 

Total. 

Aconite  and  belladonna  liniment 

I 

I 

2 

Antimony  (?)  

I 

I 

I 

Arsenic  

4 

5 

I 

2 

3 

8 

Atropine  

2 

2 

2 

Belladonna  

1 

I 

3 

4 

5 

Belladonna  liniment  

1 

1 

1 

Cantharides  

I 

Carbolic  acid  

32 

57 

'89 

6 

4 

10 

99 

1 

1 

2 

2 

3 

Chlorodyne  

1 

I 

2 

1 

3 

4 

6 

Chloroform  

1 

1 

1 

1 

2 

Cocaine  and  aconite  

1 

1 

1 

Cresolene  

2 

2 

2 

Hydrocyanic  acid  

22 

2 

24 

3 

3 

27 

Lysol  

2 

3  ^ 

3 

Mercuric  chloride;  

3 

2 

5 

2 

2 

7 

Narcotic  (kind  not  stated) .... 

1 

1 

4 

2 

6 

7 

7 

I 

8 

8 

Opium  (laudanum  and  morphine) 

37 

II 

48 

41 

17 

'58 

106 

42 

33 

75 

5 

10 

15 

90 

Paregoric  

1 

1 

Potassium  cyanide  

33 

3 

36 

5 

5 

41 

Strychnine  

7 

6 

13 

1 

3 

4 

17 

Sulphonal  

2 

2 

2 

1 

2 

2 

1 

1 

1 

1 

2 

1 

1 

I 

Total  

198 

125 

323 

75 

49 

124 

447 

124 


Sale  of  Bichloride  Tablets. 


Am.  Jour.  Pharm. 
March,  1914. 


Suicides  and  accidental  deaths  from  non-scheduled  substances  reported  by  the 
registrar-general  of  births,  deaths,  and  marriages  for  England 
and  Wales  for  the  year  iqii. 


Poison. 


Acetanilide  

Acetic  acid  

Alcohol  

Ammonia  

Camphor  

Camphorated  oil  

Caustic  potash  

Caustic  soda  

Chloride  of  lime  

Chromic  acid  

Disinfectant  (?)  

Hartshorn  and  oil  

Hydrochloric  acid  

Liniment  (?)  

Mercury  (?)  

Methylated  spirit  

Nitric  acid  

Paraffin  

Pennyroyal  

Phosphorus  

Potassium  bichromate.  . . 
Potassium  binoxalate .  .  .  . 

Potassium  bromide  '. 

Potassium  permanganate. 

Saltpeter  

Sulphate  of  copper  

Sulphuric  acid  

Veronal  

Whisky . .  .  

Zinc  chloride  

Kind  not  stated  


39 


Total   99 


Suicides. 


Male. 


43 


Fe- 
male. 


Total. 


Accidental  deaths. 


Male. 


30 

2 


73 

2 


6o 


2 
I 

19 


83 


82 


68 


Fe- 
male. 


Total. 


47 


2 
I 

26 
I 
I 

2 

I 
I 

2 

I 
I 

2 
2 

3 
17 

i 

28 
ii5 


Total 
deaths. 


I 

2 
2 
22 
2 
2 


I 

3 
i 

99 
3 

2 
2 

4 

2 
10 

4 
4 
i 

3 

2 


19 
i 
i 

88 
297 


of  the  United  States  upward  of  5000  deaths  from  acute  poisoning 
are  reported  annually,  even  these  apparently  large  figures  are  sug- 
gestive as  being  comparable  with  those  included  in  the  appended 
tables  copied  from  the  report  of  the  registrar-general  for  England 
and  Wales. 

Corrosive  mercuric  chloride  was  introduced  as  an  antiseptic  in 
surgical  procedure  more  than  30  years  ago,  and  for  two  decades  at 
least  was  widely  known  by  the  popular  names  "  corrosive  sublimate," 
"  bichloride,"  or  "  sublimate,"  and  used  in  the  form  of  solutions  for 
a  variety  of  purposes.    This  widespread  use  led  to  its  employment 


AmMaJrXm4.rm'j  Sale  °f  Bichloride  Tablets.  125 

in  other  directions,  so  that  at  the  present  time  the  statement  made 
by  the  governor  of  Pennsylvania  that  bichloride  of  mercury  "  is  a 
household  commodity  "  is  altogether  too  true,  particularly  of  the 
tablets — pounds,  if  not  tons,  of  which  are  sold  annually  for  other 
than  medicinal  purposes. 

A  survey  of  the  current  price  lists  of  five  of  the  larger  manufac- 
turers of  pharmaceutical  preparations  in  the  United  States,  presents 
some  rather  startling  information,  and  suggests  a  really  valid  reason 
why  tablets  of  corrosive  mercuric  chloride  may  be  considered  to  be 
more  important  factors  in  the  health  and  welfare  of  many  members 
of  the  community  than  is  generally  supposed.  Perhaps  the  most 
startling  discovery  is  the  fact  that  not  a  single  manufacturer  of 
tablets  of  corrosive  mercuric  chloride  markets  them  under  a  name 
properly  indicating  the  nature  of  the  materials  contained  therein. 
In  the  lists  referred  to  we  find,  under  corrosive  sublimate,  mercuric 
chloride  or  mercury  bichloride,  a  cross  reference  to  antiseptic  tablets 
or  antiseptics,  and  under  this  heading  the  several  price  lists  men- 
tioned would  present  the  following  composite  table : 

A  composite  list  of  antiseptic  tablets  from  the  current  price  lists  of  five  leading 

manufacturers. 

Antiseptic  disks. — Compressed.  Green  or  white.  Corrosive  mercuric 
chloride  0.5  gm.  with  ammonium  chloride. 

Antiseptic  tablets. — Compressed.  White,  blue,  green,  red,  or  pink.  Cor- 
rosive mercuric  chloride  0.5  gm.  with  ammonium  chloride. 

Antiseptic  tablets. — White,  blue,  green,  or  red.,  Corrosive  mercuric 
chloride  0.5  gm.  with  sodium  chloride. 

Antiseptic  tablets,  alkaline. — White,  or  pink.  Sodium  borate,  sodium 
bicarbonate,  sodium  salicylate,  sodium  benzoate,  sodium  chloride,  oil  of  euca- 
lyptus, thymol,  menthol,  oil  of  gaultheria. 

Antiseptic  tablets,  alkaline,  effervescent: — White  or  pink  (?).  These  tab- 
lets are  superior  to  those  usually  sold,  which  harden  with  age  and  dissolve 
with  difficulty. 

Antiseptic  tablets,  alkaline,  improved. — White  or  pink.  Formula  same 
as  alkaline  antiseptic  tablets  with  addition  of  hydrastine  hydrochloride  and 
sanguinarine  nitrate. 

Antiseptic  alkaline,  improved. — Valuable  as  an  injection  in  urethritis, 
vaginitis,  and  all  diseases  of  the  urethral  and  vaginal  passages  requiring  a 
mild  antiseptic  and  deodorant. 

Antiseptic  tablets,  Bernays,  small. — White,  blue,  or  pink.  Corrosive  mer- 
curic chloride  0.125  gm.  with  citric  acid. 

Antiseptic  tablets,  Bernays,  large. — White,  blue,  or  red.  Corrosive  mer- 
curic chloride  0.5  gm.  with  citric  acid. 


126 


Sale  of  Bichloride  Tablets. 


i  Am.  Jour.  Pharm. 
1      March,  1914. 


Antiseptic  tablets,  Bernays,  special  large. — White  or  blue.  Corrosive 
mercuric  chloride  0.45  gm.  with  citric  acid. 

Antiseptic  tablets,  Clover. — White,  blue,  or  pink.  Corrosive  mercuric 
chloride  0.45  gm.  with  citric  acid. 

Antiseptic  tablets,  cyanide. — White  or  pink.  Mercuric  cyanide  0.5  gm. 
with  sodium  borate. 

Antiseptic  tablets,  detergent. — Sodium  bicarbonate,  sodium  borate,  sodium 
salicylate,  eucalyptol,  menthol,  and  oil  of  wintergreen. 

Antiseptic  tablets,  detergent,  improved. — Contain  in  addition  to  the  in- 
gredients mentioned  above,  sanguinarine  nitrate  and  hydrastine  hydro- 
chloride. 

Antiseptic  tablets,  diamond. — White,  blue,  or  pink.  Corrosive  mercuric 
chloride  0.5  or  0.125  gm.  with  citric  acid. 

Antiseptic  tablets,  external. — White,  green,  pink,  or  blue.  Corrosive 
mercuric  chloride  0.5  gm.  with  ammonium  chloride. 

Antiseptic  tablets,  La  Place. — Corrosive  mercuric  chloride  0.25  gm.  with 
tartaric  acid. 

Antiseptic  tablets,  mercuric  bichloride,  Young's. — Blue.    Nine  varieties. 

Antiseptic  tablets,  mercury  cyanide. — White  or  pink.  Mercuric  cyanide 
0.5  gm.  with  sodium  borate. 

Antiseptic  tablets  No.  3. — White  or  pink.  Mercuric  cyanide  0.5  gm.  with 
borax. 

Antiseptic  tablets,  St.  J.  Perry. — White  or  pink.  Mercuric  cyanide  0.5  gm. 
with  ammonium  chloride. 

Antiseptic  tablets  No.  6. — Very  soluble.  White  or  blue.  Corrosive  mer- 
curic chloride  0.5  gm.  with  citric  acid. 

Antiseptic  tablets,  potassium  permanganate. — Compressed.    Five  varieties. 

Antiseptic  tablets,  St.  J.  Perry. — White  or  pink.  Mercuric  cyanide  0.5  gm. 
with  borax. 

Antiseptic  tablets,  tartacid  sublimate. — Corrosive  mercuric  chloride  0.25 
gm.  with  tartaric  acid. 

Antiseptic  tablets,  Young's. — Blue.  Corrosive  mercuric  chloride."  Nine 
varieties. 

Antiseptic  tablets,  Wilson's. — White,  green,  pink,  or  blue.  •  Corrosive  mer- 
curic chloride  0.5  gm.  with  ammonium  chloride. 

The  tablets  in  this  list  containing  corrosive  mercuric  chloride  are 
marketed  in  16  varying  sizes,  5  different  shapes,  and  5  different 
colors.  Three  of  the  shapes  are  distinctive  and  probably  proprietary 
in  nature.  Obviously  the  most  objectionable  feature  is  the  con- 
fusion which  may  arise  from  the  totally  misleading  name  applied  to 
tablets  containing  highly  toxic  materials. 

The  possible  abuse  arising  from  the  use  of  a  totally  misleading 
name  for  poisonous  substances  is  further  emphasized  by  the  state- 
ment recently  made  by  one  of  the  agitators  for  legislation  to  provide 
a  distinctive  shape  for  "  antiseptic  tablets."  This  writer  says :  "  It 
is  a  known  fact  that  the  tablets  of  corrosive  sublimate  are  very  easily 


AmMaJrh?iP9i4m-}         Sale  of  Bichloride  Tablets.  127 

procured,  and  are  used  to  a  very  large  extent  as  a  home  remedy, 
hence  they  are  not  looked  upon  as  the  dangerous  agents  that  they 
really  are  in  the  hands  of  the  careless  and  ignorant." 

Among  the  many  suggestions  that  have  been  made  to  compel 
uniformity  in  shape  and  size  of  tablets  of  corrosive  mercuric  chloride, 
we  have  proposals  to  have  them  triangular,  coffin-shaped,  kidney- 
shaped,  and  in  the  shape  of  a  skull,  in  addition  to  the  various  forms 
already  in  use.  Suggestions  have  also  been  made  to  enact  laws  to 
compel  manufacturers  to  color  these  tablets  red,  green,  blue,  yellow, 
and  pink;  also  to  give  them  a  distinctive  odor,  and  to  compel  their 
being  dispensed  in  a  uniform  and  distinctively  shaped  bottle ;  all  of 
which,  if  it  were  practicable  to  enforce  uniformity  in  all  States  and 
with  all  manufacturers,  would  at  best  tend  to  elaborate  on  the 
misuse  of  tablets  of  this  kind,  rather  than  to  prevent  accident,  or 
their  use  as  a  poison  for  suicidal  purposes. 

Even  at  the  present  time  there  is  sufficient  legislation,  if  en- 
forced, to  serve  as  a  reasonable  safeguard  in  connection  with  the 
sale  of  corrosive  mercuric  chloride  at  retail.  No  less  than  38  States 
include  corrosive  sublimate  specifically  in  the  laws  designed  to  restrict 
the  sale  of  poisons,  and  in  but  one  of  the  existing  laws,  that  of  Utah, 
are  corrosive  sublimate  tablets  exempted  from  registration  in  the 
poison  register,  otherwise  uniformly  required  for  the  sale  of  cor- 
rosive sublimate  itself.  During  the  present  year,  three  States, 
Oregon,  Nevada,  and  California,  have  enacted  modified  poison  laws 
and  specifically  enumerate  tablets  of  corrosive  sublimate  as  belong- 
ing in  "  Schedule  A,"  drugs,  the  sale  of  which  is  required  to  be 
registered  in  a  book  provided  for  that  purpose.  These  several  States 
also  specifically  enumerate  "  antiseptic  tablets  containing  corrosive 
sublimate,"  being,  so  far,  the  only  States  recognizing  the  present-day 
custom  of  labelling  these  very  toxic  preparations,  "  antiseptic 
tablets." 

In  addition  to  specific  agitation  for  the  proper  labelling  of  all 
preparations  containing  poisonous  substances,  the  most  promising 
innovation  is  the  suggestion  that  a  type  form  of  corrosive  mercuric 
chloride  tablet  or  pastille  be  introduced  in  the  Pharmacopoeia  of  the 
United  States,  with  a  view  of  providing  adequate  safeguards  to  pre- 
vent accidental  poisonings.  While  the  suggestions  that  have  been 
made  for  this  purpose  are  many  and  varied,  it  would  appear  that, 
in  view  of  the  rapidly  growing  intercourse  between  the  different 
countries  of  the  world,  it  might  be  desirable  to  secure  international 
uniformity  in  regard  to  preparations  of  this  type.    It  has  been  pro- 


128 


Progress  in  Pharmacy* 


f  Am.  Jour.  Pharm. 
\     March,  1914. 


posed,  unless  specific  and  valid  objections  could  be  offered,  to  adopt 
for  inclusion  in  the  Pharmacopoeia  of  the  United  States  the  descrip- 
tion of  mercuric  chloride  pastilles  included  in  the  German  Pharma- 
copoeia. This  latter  Pharmacopoeia  provides  that  pastilles  of  mer- 
curic chloride  consist  of  equal  parts  of  corrosive  mercuric  chloride 
and  sodium  chloride,  and  requires  that  the  pastilles  be  colored  bright 
red  with  aniline  dye,  have  a  cylindrical  shape,  and  be  twice  as  long 
as  thick.  These  tablets  or  pastilles  must  be  wrapped  individually  in 
black  paper,  bearing  the  German  equivalent  of  the  word  poison  in 
white  letters.  The  weight  of  a  tablet  must  be  stated,  and  the 
wrapped  tablet  is  to  be  dispensed  only  in  suitable  glass  bottles  or 
tubes. 

As  an  argument  for  including  in  the  Pharmacopoeia  of  the  United 
States  an  official  tablet  of  corrosive  mercuric  chloride,  rather  than 
enacting  legislation  to  compel  uniformity  in  the  shape,  size,  color, 
and  odor  of  all  tablets  containing  corrosive  mercuric  chloride,  it  has 
been  pointed  out  that  inclusion  in  the  Pharmacopoeia  would  not  in 
any  way  interfere  with  the  legitimately  established  trade  of  manu- 
facturers, but  would  tend  to  discourage  the  sale  and  use  of  such 
preparations  and  bring  about  the  gradual  popularization  of  the 
official  tablet.  If,  in  addition  to  this,  it  were  practicable  to  induce 
manufacturers  properly  to  label  all  of  their  preparations  so  as  to 
indicate  the  presence  of  any  highly  toxic  substance,  and  then  to  sug- 
gest to  purchasers  of  tablets  of  this  kind  the  need  for  keeping  them 
apart  or  in  such  a  way  that  they  could  not  readily  be  mistaken  for 
other  nontoxic  preparations,  little  or  no  additional  legislation  would 
be  necessary,  unless  it  were  to  restrict  newspapers  from  publishing 
unnecessary  details  in  regard  to  the  nature  and  kind  of  poison  used 
in  cases  of  accidental  or  intentional  poisoning. 


PROGRESS  IN  PHARMACY. 

A  Quarterly  Review  of  Some  of  the  More  Interesting  Litera- 
ture Relating  to  Pharmacy  and  Materia  Medica. 

By  M.  I.  Wilbert,  Washington,  D.  C. 

An  unusual  amount  of  activity  is  being  reflected  in  current 
pharmaceutical  and  drug  journals.  While  much  of  this  activity  is 
more  or  less  closely  related  to  renewed  interest  in  the  revision  of 
the  Pharmacopoeia,  awakened  by  the  publication  of  the  first  instal- 


Am.  Jour.  Pharm.  ) 
March,  1914.  / 


Progress  in  Pharmacy. 


129 


ment  of  Abstracts  of  Proposed  Changes,  with  New  Standards  and 
Descriptions  to  be  included  in  the  U.  S.  P.  IX,  legislation  and  the 
prospective  meetings  of  national  and  state  associations  are  also 
being  actively  discussed  in  all  sections  of  the  country. 

Looking  Ahead. — The  editor  of  the  Bulletin  of  Pharmacy  sug- 
gests some  reform  measures  for  the  A.  Ph.  A.,  which  deserve  the 
careful  attention  and  the  hearty  co-operation  of  every  member  of 
that  association.  The  proposed  reforms  of  immediate  interest  con- 
cern the  coming  meeting  of  the  A.  Ph.  A.,  more  particularly  the 
program  of  section  meetings.  Not  the  least  important  of  the  sug- 
gestions made  is  the  proposition  to  have  the  Council  meeting  held 
in  the  evenings  so  as  to  eliminate  the  constantly  increasing  interfer- 
ence of  the  Council  meetings  with  the  meetings  of  the  sections. 
Another  proposition  of  considerable  interest  is  the  suggestion  to 
restrict  the  scientific  meetings  of  the  Association  sections  to  two 
sessions  a  day.  The  third  proposition  is  to  eliminate  from  the  now 
existing  sections  such  as  do  not  warrant  continuance  and  thus  restrict 
the  scientific  business  of  the  Association  to  simultaneous  sessions 
of  a  limited  number  of  sections  for  a  sufficient  number  of  days  to 
transact  all  of  the  business  in  hand.  If  in  addition  to  these  several 
reforms  the  unnecessary  interference  by  entertainment  features  could 
be  eliminated,  there  is  no  reason  why  the  meetings  of  the  American 
Pharmaceutical  Association  should  not  be  held  as  are  the  meetings 
of  the  American  Medical  Association,  in  from  3  to  4  days,  allowing 
the  additional  days  of  the  week  for  entertainments  or  for  the  meet- 
ings of  correlated  societies  and  associations  that  choose  to  convene  at 
or  about  the  same  time  that  the  American  Pharmaceutical  Associa- 
tion does.  Mr.  Mason  truthfully  says  that  the  existing  trouble  with 
the  A.  Ph.  A.  "  arises  from  too  much  energy  instead  of  too  little, 
and  what  is  needed  is  that  this  energy  in  its  manifold  manifestations 
be  harnessed  up  and  co-ordinated  in  a  more  intelligent  manner. 
.  .  .  The  situation  at  Nashville  last  August  was  one  of  confusion 
worse  confounded.  There  were  the  seven  regular  sections  of  the 
Association,  each  holding  two  or  three  sessions.  There  was  the 
annual  meeting  of  the  National  Association  of  Boards  of  Pharmacy 
with  four  or  five  sessions.  There  was  the  annual  meeting  of  the 
Conference  of  Pharmaceutical  Faculties,  and  the  joint  conference 
of  the  section  on  Education  and  Legislation  of  the  A.  Ph.  A.  . 
With  it  all  there  was  no  let-up  in  the  work  from  nine  o'clock  in  the 
morning  until  one  or  two  o'clock  the  next  morning.    Everybody  was 


130 


Progress  in  Pharmacy. 


{Am.  Jour.  Pharm. 
March,  1914. 


tired  out.  Everybody  was  more  or  less  befuddled  by  the  multiplicity 
of  business.  .  .  .  The  A.  Ph.  A.  has  outgrown  the  clothes  of 
a  growing  youth  and  now  needs  the  equipment  of  the  adult  it  has 
come  to  be.  Particularly  are  the  annual  meetings  in  need  of  reform 
if  they  are  successfully,  intelligently  and  efficiently  to  handle  the 
vast  amount  of  work  undertaken  by  the  Association." — Bull.  Pharm., 
1 9 14,  v.  28,  pp.  67-70. 

Drijg  Trades'  Conference. — A  meeting  of  the  National  Drug 
Trades'  Conference  was  held  at  Washington,  January  12  to  14,  all 
of  the  several  national  organizations  being  represented.  Among  the 
resolutions  adopted  by  the  Conference  were : 

One  asking  newspapers  to  omit  as  far  as  possible  all  detail  of 
poisons  or  other  instruments  employed  in  suicide  and  murder. 

One  recommending  that  legislation  relating  to  methods  of  pack- 
ing and  labelling  of  corrosive  mercuric  chloride  tablets  and  other 
dangerous  toxic  drugs  be  deferred,  pending  a  report  by  the  Commit- 
tees of  Revision  of  the  Pharmacopoeia  and  the  National  Formulary, 
and  tendering  such  aid  as  the  members  of  the  conference  may  be  in 
a  position  to  give  in  making  the  revision,  in  order  that  suitable  regula- 
tion with  respect  to  these  drugs  may  be  made. 

One  requesting  the  Postmaster-General  to  change  paragraph  5 
of  section  472  of  the  postal  regulations,  so  as  to  permit  the  mailing 
as  first-class  matter  of  poisonous  substances  packed  in  metal  con- 
tainers, bearing  the  name  of  the  sender  and  the  word  "  Poison." 

One  requesting  that  the  Committee  of  Revision  of  the  United 
States  Pharmacopoeia  consider  the  desirability  of  inserting  in  the 
forthcoming  revision  of  the  United  States  Pharmacopoeia  a  section 
defining  the  word  "  poison." — Drug.  Circ,  1914,  v.  58,  p.  99. 

Poison  Bottles. — Anon.  The  use  of  a  special  bottle  for  poisons 
is  not  enforced  by  law  in  the  United  States,  although  legislation  em- 
bodying the  principle  has  more  than  once  been  attempted  in  various 
States.  On  what  grounds  the  proposals  have  been  rejected  we  can- 
not understand,  for  there  is  ample  proof  in  the  experience  of  our 
own  country  that  the  "  poison  bottle  "  is  an  excellent  danger  signal. — 
Pharm.  J.,  19 14,  v.  92,  p.  89. 

Restriction  of  Sale  of  Coal-tar  Synthetics. — The  Kansas 
City  Association  of  Retail  Druggists  is  conducting  an  energetic 
movement  toward  legislation  prohibiting  the  sale  of  antipyrin,  acet- 
phenetidin,  and  acetanilide,  except  on  physicians'  prescriptions. — 
Drug.  Circ,  19 14,  v.  58,  p.  103. 


Am.  Jour.  Pharm.  ) 
March,  1914.  f 


Progress  in  Pharmacy. 


Drug  Store  Strike. — The  advantages  of  efficient  organization 
and  co-operation  are  well  emphasized  in  a  recent  number  of  the  Phar- 
mazeutische  Post  (December  24,  1913,  v.  46,  pp.  1109-1112),  which 
publishes  an  illustrated  description  of  a  successful  drug  store  strike 
in  Argentine  brought  about  by  a  proposal  to  increase  the  stamp  tax 
on  specialties  and  perfumery,  and  to  impose  a  complicated  method 
of  control  which  the  druggists  of  Argentine  considered  impracticable. 
The  strike  was  general,  every  drug  store  in  Argentine  closing  on  a 
given  date  and  the  concerted  action  promptly  resulted  in  the  law 
being  set  aside  for  the  time  being  and  subsequently  revised. 

Useful  Drugs. — An  editorial  designates  the  recently  published 
volume  on  Useful  Drugs  as  a  book  with  a  purpose  that  will  mark 
an  era  in  American  medicine  and  will  likewise  have  a  distinct  effect 
upon  American  pharmacy.  The  editor  criticizes  the  inclusion  of 
syrup  of  sarsaparilla  on  the  mistaken  supposition  that  its  use  is 
recommended  as  a  vehicle  but  concludes  that  even  this  is  a  minor 
matter  and  Useful  Drugs  has  a  purpose  and  also  has  a  future. — 
Drug.  Circ,  1914,  v.  58,  p.  66. 

In  a  book  review,  p.  98,  the  same  journal  adds :  "  Useful  Drugs 
can  therefore  be  described  as  the  ideal  epitome,  and  the  pharmacist 
interested  in  his  prescription  department  will  do  well  to  aid  in  the 
circulation  of  the  work  by  distributing  it  among  physicians  of  his 
own  neighborhood." 

Digest  of  Comments  on  the  Pharmacopoeia  of  the  United 
States  of  America. — A  book  review  of  Hyg.  Lab.  Bull.,  No.  87,  says 
in  part :  "  In  the  period  covered  by  this,  the  seventh  in  the  series  of 
'  Digests,'  the  critical  character  of  the  comments  on  the  German  Phar- 
macopoeia might  be  taken  to  indicate  that  the  makers  of  pharmaco- 
poeias must  in  the  future  cater  to  a  more  and  more  discriminating 
constituency.  This  attitude  on  the  part  of  users  of  pharmacopoeias  is 
still  further  emphasized  by  the  growing  demand  for  a  limited  materia 
medica  and,  by  inference,  the  limitation  of  the  scope  of  the  pharma- 
copoeia to  substances  of  recognized  therapeutic  efficacy  and  sub- 
stances which,  to  some  degree  at  least,  lend  themselves  to  adequate 
standardization,  whether  chemical  or  physiologic. — /.  Am.  M.  Assoc., 
v.  61,  p.  2005. 

Japanese  Pharmacopoeia. — A  new  revision  of  the  monographs 
of  the  Ph.  Japon  III  is  announced  as  taking  effect  December  27,  1913. 
The  changes  involve  acetylsalicylic  acid,  lanolin  and  oil  of  sandal- 
wood.— Chem.  and  Drug.,  1914,  v.  84,  p.  167. 


132 


Progress  in  Pharmacy. 


J  Am.  Jour.  Pharm. 
\     March,  1914. 


Ph.  Brit. — The  British  Pharmacopoeia  Committee  reports  that 
"  Two  further  sections  of  the  text  of  the  new  Pharmacopoeia  have 
been  prepared  by  the  editors,  and  have  been  submitted  to  the  Com- 
mittee and  to  the  several  Committees  of  Reference.  All  the  sections 
so  prepared  have  been  sent  to  press  and  are  at  present  in  type, 
undergoing  revision.  It  is  hoped  that  the  appendix,  and  the  con- 
cluding parts  of  the  draft,  will  be  ready  for  consideration  early  in 
the  new  year." — Pharm.  J.,  1913,  v.  91,  p.  849. 

Pharmacopceal  Doses. — An  editorial,  in  commenting  on  a  propo- 
sition, recently  made  in  the  Medical  Press  of  Great  Britain,  to  adjust 
the  strength  of  tinctures  so  that  the  doses  of  various  groups  distin- 
guished by  prefixing  "  per  "  and  "  sub  "  would  be  the  same,  says : 
"  Pharmaceutical^  the  strength  of  tinctures  is  only  of  importance 
when  regarded  from  the  point  of  view  of  providing  sufficient  men- 
struum adequately  to  exhaust  a  drug."  "  In  regard  to  the  sugges- 
tion as  to  names  the  question  arises  in  connection  with  subtinctures, 
will  the  alcohol  or  the  drug  in  the  tincture  be  the  more  grateful  and 
comforting  to  the  patient?" — Chem.  and  Drug.,  1914,  v.  84,  pp. 
19-20. 

Proprietary  Medicines  in  Great  Britain. — Xrayser  II,  com- 
menting on  the  first  year  of  medical  benefit  under  the  insurance  act  in 
Great  Britain,  asserts  that  it  has  brought  with  it  a  marked  change 
in  the  nature  of  business  done  by  chemists  and  druggists.  One  man 
reports  that  he  will  dispense  10,000  prescriptions  and  upon  the  whole 
he  is  satisfied  from  the  profit  realized  directly  from  this  source.  The 
increase  in  the  prescription  business  is  further  notable  for  the  fact 
that  the  trade  in  proprietaries  has  considerably  decreased  and  should 
mean  that  chemists  as  a  whole  are  enjoying,  and  will  continue  to 
enjoy,  the  increase  in  what  is  after  dispensing  the  most  profitable 
department  of  their  business. — Chem.  and  Drug.,  19 14,  v.  84,  p.  85. 

Historical  Medical  Museum. — An  unsigned  article  presents  a 
number  of  illustrations  of  the  Historical  Medical  Exhibition  in  Wig- 
more  Street,  London,  which  was  organized  by  Henry  S.  Wellcome 
and  opened  on  the  occasion  of  the  International  Medical  Congress  dur- 
ing last  summer.  This  museum  is  now  being  rearranged  as  a  perma- 
nent institution  and  there  is  probably  nothing  in  existence  elsewhere 
which  is  quite  like  the  collection  which  will  shortly  be  available  for 
the  use  of  students  and  others  interested  in  the  study  of  antiquarian 
medicine  and  surgery.  The  illustrations  include  a  reproduction  of 
the  exterior  of  a  London  apothecary's  shop  of  the  17th  Century, 


Am.  Jour.  Pharm.  \ 
March,  1914.  J 


Progress  in  Pharmacy. 


133 


"  At  the  sign  of  '  Ye  wild  man/  "  a  reproduction  of  Liebig's 
laboratory  at  Giessen,  and  the  interior  of  an  Italian  pharmacy  of 
the  1 6th  Century. — Pharm.  J.,  191 3,  v.  91,  pp.  944-945. 

History  of  Pharmacy. — The  Chemist  and  Druggist,  January  31, 
1 9 14,  v.  84,  p.  183,  announces  that  an  arrangement  has  been  made 
with  the  publishers  of  the  "  Chronicles  of  Pharmacy,"  by  the  late 
A.  C.  Wooton,  which  enables  that  journal  to  offer  this  book  in  two 
volumes  at  7s.  6d.,  carriage  paid  in  the  United  Kingdom,  or  8's.  post 
free  to  any  part  abroad.  This  exceptional  offer  should  popularize 
the  book  and  make  it  available  to  all  pharmacists  who  are  in  any 
way  interested  in  the  history  of  their  craft.  Orders  for  the  volumes 
should  be  addressed  to  the  book  department  of  the  Chemist  and  Drug- 
gist, 42  Cannon  Street,  London,  E.  C. 

Friedmann  Institutes  are  being  organized  in  various  parts  of 
the  country  and  the  personnel  of  these  organizations  in  practically 
every  instance  is  sufficient  to  suggest  their  true  nature.  Steps  have 
been  taken  in  several  states  to  check  this  exploitation  of  the  consump- 
tive for  commercial  gain.  But  what  is  most  needed  is  that  these 
unscrupulous  attempts  should  be  met  with  an  intensive  campaign 
of  education  of  the  public  concerning  the  dangers  and  worthlessness 
of  this  treatment. — /.  Am.  M.  Assoc.,  1913,  v.  61,  p.  1050. 

U.  S.  Patent  for  a  Complex  Medicine. — An  editorial  calls  at- 
tention to  U.  S.  Patent  1,081,069,  granted  December  9,  191 3,  for  a 
mixture  of  excretory  constituents — creatinin,  guanidin,  and  allan- 
toin — to  be  used  as  a  specific  in  a  number  of  microbial  infections 
and  illnesses.  The  editorial  states  that  the  granting  of  a  patent  on 
the  claims  made  should  be  sufficient  to  show  the  need  of  change  in 
the  method  of  granting  patents,  at  least  in  the  methods  governing 
the  issuance  of  patents  for  medicinal  products. — /.  Am.  M.  Assoc., 
1914,  v.  62,  pp.  54-55. 

Aloes. — Tutin  and  Naunton  report  an  investigation  to  ascertain 
if  any  anthraquinone  derivative  other  than  aloe-emodin  is  contained 
in  aloes.  They  were  unable  to  isolate  such  compounds  as  emodin 
and  chrysophanol  but  found  several  samples  of  aloes  which  contained 
aloe-emodin  as  an  impurity. — Pharm.  J.,  1913,  v.  91,  p.  836. 

Alypin,  Misleading  Advertisement  of. — Bruck,  F.,  called  at- 
tention four  years  ago  to  the  misleading  statements  in  the  advertising 
of  alypin.  Both  an  anaesthetic  and  blood-expelling  action  are  claimed 
for  it  but  in  reality  it  has  none  of  the  latter.  It  is  also  stated  that 
alypin  is  considerably  less  toxic  than  cocaine,  while  Schroder  and 


134 


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\     March,  1914. 


others  have  found  that  it  is  fully  as  toxic  as  cocaine  and  the  last  sup- 
plement to  the  German  Pharmacopoeia  gives  the  maximum  dose  the 
same  for  both  alypin  and  cocaine. — Therap.  Monatsh.,  Berlin,  1913, 
v.  27,  p.  787. 

Arheol  is  a  proprietory  name  for  santalol,  C15H26OH,  a  sequi- 
terpenic  alcohol,  the  chief  constituent  of  sandalwood.  Arheol  is 
a  colorless,  oily  liquid;  specific  gravity,  0.979  at  150  C.  It  is  in- 
soluble in  water  but  soluble  in  alcohol.  It  boils  under  1 1  mm.  pres- 
sure at  1690,  and  under  ordinary  pressure  at  about  5000  C. — /.  Am. 
M.  Assoc.,  1913,  v.  61,  p.  1900. 

Atophan,  Secondary  Effects  of. — Phillips,  John, calls  attention 
to  the  occurrence  of  various  skin  rashes  caused  by  the  administra- 
tion of  atophan  and  reports  5  cases.  These  rashes  resemble  those 
following  the  administration  of  antipyrine  and  indicate  that  atophan 
should  not  be  given  in  the  treatment  of  urticaria  as  has  been  advised. 
— /.  Am.  M.  Assoc.,  1913,  v.  61,  p.  1040. 

Behring's  Diphtheria  Vaccine. — Kissling,  K.,  reports  on  the 
application  of  Behring's  new  vaccine  to  immunize  children  who  had 
been  exposed  to  diphtheria  in  different  wards  of  the  Hamburg 
general  hospital.  Of  the  310  children  treated,  111  were  given  a  sec- 
ond injection  and  none  of  this  group  has  contracted  diphtheria,  and 
only  8  among  the  remaining  199.  In  these  cases  the  patients  were 
convalescing  from  scarlet  fever  and  the  diphtheria  was  exceptionally 
mild,  or  the  vaccine  did  not  have  time  to  act  before  the  diphtheria 
developed ;  several  days  are  required  for  the  vaccine  to  complete 
the  immunization.  Adults  respond  with  more  of  a  reaction  to  the 
vaccine  than  children.  Pre-existing  disease  of  any  kind  does  not 
seem  to  be  a  contra-indication.  (Deutsch.  med.  Wchnschr.,  1913, 
v.  39,  No.  51.) — /.  Am.  M.  Assoc.,  1914,  v.  62,  p.  418. 

Cereus  Grandiflorus. — Grober,  A.  Many  contradictory  state- 
ments have  been  published  as  to  the  activity  of  Cactus  grandiflorus 
and  its  value  as  a  heart  remedy.  The  pharmacological  experiments 
of  the  author  show  that  the  drug  exerts  some  action  on  the  frog's 
heart  similar  to  digitalis.  This  may  be  attributed  to  the  glucoside 
present  as  well  as  to  the  alkaloid.  The  amount  of  active  principles 
present  in  the  drug  is,  however,  so  small,  that  it  cannot  be  consid- 
ered in  any  way  as  a  substitute  for  digitalis  in  human  therapeutics. — 
Therap.  Monatsh.,  1913,  v.  27,  pp.  580-581. 

Chromium  Sulphate. — Kolipinski,  S.,  is  quoted  as  saying: 
"  The  diseases  in  which  chromium  has  been  used  with  success  are : 


Am.  Jour.  Pharni.  ) 
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135 


cirrhosis  of  the  female  breast,  castration,  menopause,  functional  im- 
potency  in  men,  chronic  alcoholism,  nervous  vomiting  and  vomiting 
in  pregnancy,  neurasthenia,  locomotor  ataxia,  exophthalmic  goiter 
and  the  migraines." — /.  Am.  M.  Assoc.,  19 13,  v.  61,  p.  192 1. 

CUNILA    MARIANA    L.,    A    SUBSTITUTE    FOR    SpIGELIA.  StOCk- 

berger,  W.  W.  Several  samples  offered  as  pink  root,  recently  sub- 
mitted by  dealers  in  crude  drugs,  were  found  on  investigation  to  be 
spurious  and  to  consist  largely  of  Cunila  mariana  L. — /.  Am.  Pharm. 
Assoc.,  1914,  v.  3,  pp.  33-34. 

Cusylol. — Cusylol  is  a  soluble  form  of  copper  citrate,  intro- 
duced for  use  in  ophthalmic  work.  It  is  a  blue  crystalline  powder, 
soluble  about  1 :  3  in  water.  The  powder  is  stable.  Solutions  above 
1 :  1,000  in  strength  do  not  keep  well,  since  they  attack  some  kinds 
of  glass  with  the  formation  of  a  flocculent  deposit. — Pharm.  J.,  igi4, 
v.  92,  p.  136. 

Digipan,  according  to  the  manufacturers,  represents,  with  the 
exception  of  digitonin,  all  of  the  glucosides  of  digitalis  leaves, 
obtainable  by  extraction  at  not  exceeding  300. — Sudd.  Apoth.-Ztg., 
1913*  v.  53,  p.  833. 

Diogenal  is  a  new  sedative  related  to  veronal.  Chemically  it  is 
dibrom-propyl-diethyl-barbituric  acid,  C11H16Br2N202.  It  is  a  white 
crystalline  powder  melting  at  1260.  The  average  dose  is  15  grains. — 
Chem.  and  Drug.,  1914,  v.  84,  p.  37. 

Echinacea. — Anon.  Echinacea  has  been  claimed  to  be  a 
"  specific  "  for  rattlesnake  bite,  syphilis,  typhoid  fever,  malaria,  diph- 
theria and  hydrophobia.  Later  enthusiasts  have  credited  it  with 
equally  certain  curative  effects  in  tuberculosis,  tetanus  and  exoph- 
thalmic goiter,  and  with  power  of  retarding  the  development  of  can- 
cer. On  the  basis  of  the  available  evidence  the  Council  on  Pharmacy 
and  Chemistry  decided  that  echinacea  was  not  worthy  of  recognition 
as  a  drug  of  probable  value.  Accordingly  it  voted  not  to  describe 
the  drug  in  New  and  Non-official  Remedies  ( The  Journal,  Nov.  27, 
1909,  p.  1836).  So  far  as  can  be  learned  no  reliable  evidence  for  the 
claims  made  for  this  drug  has  been  presented  since  the  Council  de- 
cided that  the  available  evidence  did  not  entitle  it  to  a  place  in  New 
and  Non-official  Remedies. — /.  Am.  M.  Assoc.,  v.  61,  p.  2089. 

Elarson  is  the  strontium  salt  of  chlorarsenobehenolic  acid,  con- 
taining about  13  per  cent,  of  elementary  arsenic  and  about  6  per 
cent,  of  chloride.  It  occurs  as  an  almost  white,  amorphous,  tasteless 
powder,  insoluble  in  water  but  slightly  soluble  in  alcohol  and  ether. 


136 


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\     March,  1914. 


The  average  adult  dose  of  elarson  is  0.008  gm.  grain),  three  to 
five  times  daily,  best  taken  about  an  hour  after  meals. — /.  Am.  M. 
Assoc.,  1914,  v.  62,  p.  379. 

Emetine  Hydrochloride. — Korns,  John  H.  Emetine  hydro- 
chloride is  the  approved  method  of  treatment  for  amoebic  dysentery 
among  missionary  physicians  in  China.  In  a  recent  report  of  17 
cases,  16  did  well  under  the  emetine  treatment,  the  1  exceptional 
case  had  been  treated  unsuccessfully  with  ipecac  powders  six  months 
previously. — /.  Am.  M.  Assoc.,  1914,  v.  62,  p.  475. 

Ergot,  according  to  Lieb,  owes  its  pharmacologic  action  to  sev- 
eral constituents ;  of  these,  ergotoxine  alone  is  specific.  Beta-imi- 
doazolyethylamin,  parahydroxyphenylethylamin,  and  the  other  sym- 
pathoninetic  amines  are  products  of  the  putrefaction  which  occurs 
during  the  manufacture  of  galenical  preparations.  Each  constituent 
has  a  distinct  pharmacologic  action ;  stimulation  of  the  uterus  is 
characteristic  of  them  all. — /.  Am.  M.  Assoc.,  1914,  v.  62,  p.  486. 

Fucitol. — Votocek  and  Potmesil.  Fucose,  the  sugar  obtained 
from  bladder-wrack,  Fucus  vesiculosus,  when  reduced  with  sodium 
amalgam,  is  converted  into  the  alcohol  fucitol.  This  new  alcohol 
crystallizes  from  ethyl  alcohol  in  silvery  leaflets  which  melt  at  153- 
1540  C.  Rhodeose  and  fucose  are  stereo-isomers,  and  the  corre- 
sponding alcohols,  fucitol  and  rhoditol,  are  respectively  laevo-  and 
dextro-rotary  to  the  same  degree.  By  mixing  the  two  alcohols  in 
equimolecular  proportions  in  hot  alcohol,  racemic  fucitol  is  obtained. 
(Berichte,  1913,  v.  46,  p.  3653.) — Pharm.  J.,  1913,  v.  91,  p.  911. 

Gitonin. — Windhaus  and  Schneckenburger  have  recently  separ- 
ated a  new  digitalis  glucoside  from  Kiliani's  digitonin.  Digitonin 
was  dissolved  in  hot  alcohol,  95  per  cent.  On  setting  aside  the  solu- 
tion for  some  weeks  an  amorphous  deposit  was  formed  containing 
the  new  glucoside.  Gitonin  is  but  sparingly  soluble  in  water,  in 
methyl,  and  in  ethyl  alcohols.  It  is  insoluble  in  acetone  and  in  ether. 
It  becomes  yellow  when  heated  to  255 0  C.  and  decomposes  at  about 
2720  C.  With  sulphuric  acid  it  gives  at  first  a  pink,  then  a  red  color. 
The  exact  formula  of  the  glucoside  has  not  yet  been  determined ; 
provisionally  it  is  given  as  C29H80O2V — Pharm.  J.,  1913,  v.  91,  p.  911. 

Hediorite  is  the  lactone  of  a-glucoheptonic  acid.  It  is  recom- 
mended, to  the  extent  of  30  gms.  per  diem,  for  diabetic  patients. 
It  forms  crystals  melting  at  145 0  to  148 °,  easily  soluble  in  water. — 
Chem.  and  Drug.,  1914,  v.  84,  p.  89. 

Hydroxyphenylethylamin. — The  pharmacologic  investigation 


Am.  Jour.  Pharm. ) 
March,  1014.  _  J 


Progress  in  Pharmacy. 


137 


of  synthetic  aromatic  amines  has  been  greatly  stimulated  by  the  dis- 
covery of  the  chemical  structure  of  epinephrine  and  the  demonstra- 
tion that  it  belongs  in  this  group  of  organic  compounds.  The  syste- 
matic testing  of  numerous  related  and  suitably  constituted  amines 
has  shown  that  in  general  they  exhibit  pressor  effects  on  the  circu- 
lation and  other  physiologic  phenomena  characteristic  of  the  effective 
agent  of  the  adrenals,  their  activity  increasing  according  as  they 
approach  the  chemical  structure  of  epinephrine.  One  of  the  most 
interesting  of  all  these  newly  investigated  products  is  hydroxyphenyl- 
ethylamin,  which  can  readily  be  prepared  from  the  protein  cleavage 
derivative  ty rosin  by  splitting  off  carbon  dioxide  from  the  molecule 
of  the  latter.  This  reaction  can  be  brought  about  by  putrefactive 
bacteria ;  and  in  truth  hydroxyphenylethylamin  has  been  detected 
among  the  products  of  putrefaction  of  proteins  and  identified  by 
Barger  among  the  pressor  principles  yielded  by  putrid  meat. — /.  Am. 
M.  Assoc.,  1914,  v.  62,  p.  46. 

Lactic  Acid  Ferments. — Puckner,  W.  A.  The  frequently 
made  assertions  that  the  lactic  acid  preparations  on  the  market  are 
worthless,  led  to  an  examination  of  the  available  commercial  prod- 
ucts. This  examination  showed  that  while  all  products  containing 
living  bacteria  are  bound  to  deteriorate,  the  preparations  examined 
were  in  viable  condition,  though,  as  was  to  be  expected,  liquid  cult- 
ures were  more  active  than  were  the  tablet  preparations.  It  was  also 
found  that  manufacturers  of  these  products  are  making  every  effort 
to  insure  the  dispensing  of  reliable  preparations  when  they  are 
ordered  by  physicians. — /.  Am.  M.  Assoc.,  191 3,  v.  61,  p.  2084. 

Liquid  Paraffin. — Peck,  J.  Wicliffe,  calls  attention  to  the  wide- 
spread use  of  liquid  paraffin  for  chronic  constipation,  in  different 
sections  of  Great  Britain,  and  to  the  possibility  of  developing  the  sale 
of  this  article  as  a  specialty.  He  also  points  out  that  there  is  a  great 
difference  in  the  viscosity  of  the  many  samples  obtained  and  that  it  is 
preferable  to  use  one  having  a  medium  specific  gravity.  The  more 
fluid  ones  are  not  so  useful  in  the  treatment  of  intestinal  stasis  and 
the  heavier  preparations  are  apt  to  be  objectionable  because  they 
do  not  easily  leave  the  mouth. — Pharm.  J.,  19 14,  v.  92,  pp.  28-29. 

Liquid  Paraffin. — Chrysopathes,  J.  G.  During  the  Balkan  war 
920  cases  of  wounds  were  dressed  with  liquid  paraffin.  In  nearly 
every  case  the  wound  healed  over  in  a  remarkably  short  time ;  even 
gaping  wounds  with  exposed  bones  began  to  heal  at  once.  The  oil, 
in  fact,  is  recommended  as  a  dressing  for  sores  of  all  kinds,  and 


i3« 


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where  there  is  severe  suppuration  the  addition  of  2  per  cent,  of  iodo- 
form improves  matters.  (Zentralbl.  filr  Chirurg.,  Leipsic,  Novem- 
ber 8,  1913.) — Pharm.  J.,  1914,  v.  92,  p.  6. 

Opium. — Mr.  Jewel,  the  American  Consul  at  Vladivostok,  re- 
ports that  poppy  culture  was  introduced  into  the  Ussuri  district  by 
Chinese,  and  in  1907  the  exports  to  China  amounted  to  7223  lbs. 
This  has  since  increased. — Pharm.  J.,  1914,  v.  92,  p.  79. 

Organic  Silver  Salts. — Rogers,  L.  With  the  exception  of 
argyrol,  all  of  the  organic  silver  compounds  tested  had  a  decided 
bactericidal  action  against  the  dysentery  bacillus  when  dissolved  in 
water,  being  effective  in  five  minutes  in  dilutions  of  1  in  2500  and 
upwards.  In  the  presence  of  a  little  broth,  however,  their  action  was 
always  weaker,  but  in  a  variable  degree. — /.  Am.  M.  Assoc.,  1914, 
v.  62,  p.  412. 

Perhydrit  is  a  combination  of  hydrogen  peroxide  with  urea, 
marketed  in  the  form  of  1  gm.  tablets  representing  from  0.34  to  0.35 
per  cent,  of  hydrogen  peroxide  and  therefore  a  solid  form  of  hydro- 
gen peroxide  which  when  dissolved  in  water  may  be  used  as  a  disin- 
fectant.— Si'idd.  Apoth.-Ztg.,  191 3,  v.  53,  p.  841. 

Phenolsulphonephthalein  is  a  product  of  the  interaction  of 
phenol  and  sulphobenzoic  acid  anhydride,  differing  from  phenol- 
phthalein  in  that  a  CO  group  of  the  latter  is  replaced  by  a  S02  group. 
Phenolsulphonephthalein  is  used  for  determining  the  functional 
activity  of  the  kidney.  When  injected  intramuscularly  or  intra- 
venously it  begins  to  be  excreted  in  normal  cases  in  from  five  to  ten 
minutes.  In  cases  of  a  deficient  functional  activity,  the  first  appear- 
ance of  its  secretion  is  delayed. — /.  Am.  M.  Assoc.,  1914,  v.  62, 
pp.  297-298. 

Phenoval  is  a-brom-isovaleryl-paraphenetidin,  (CH3)2CH.- 
CHBr.CO.NH.C6H4.OC2H5.  It  is  a  new  crystalline  compound  melt- 
ing at  1490  to  1500,  and  is  recommended  as  sedative  and  hypnotic. 
It  is  insoluble  in  water,  but  is  soluble  in  the  usual  organic  solvents. 
Its  dose  is  from  0.5  to  1.0  gm. — Chem.  and  Drug.,  1914,  v.  84,  p.  89. 

Pikrastol,  administered  in  cases  of  epilepsy,  is  dimethyloldi- 
formyl-methyleneyl-tetramethylene-pentamine,  C9H17N504.  It  is 
amorphous,  and  does  not  appear  .fo  have  a  well-defined  melting 
point. — Chem.  and  Drug.,  1914,  v.  84,  p.  37. 

Quinine. — MacGilchrist,  A.  C,  claims  that  precipitated  quinine 
base  is  the  best  all-round  form  in  which  to  administer  quinine  by 
mouth ;  it  can  be  administered  intravenously,  and  it  is  preferable  to 
any  quinine  salt  in  cases  in  which  hemoglobinuria  is  dreaded.  (Ind. 


Am.  Jour.  Pharm. ) 
March,  1914.  / 


Progress  in  Pharmacy. 


139 


/.  Medical  Research,  1913,  v.  I,  No.  2.) — /.  Am.  M.  Assoc.,  1914, 
v.  62,  p.  413. 

Quinine  and  Urea  Hydrochloride. — Cables,  H.  A.,  reports 
eight  cases  of  sciatica  treated  by  hypodermic  injections  of  a  four 
per  cent,  solution  of  quinine  and  urea  hydrochloride  in  normal  salt 
solution.  There  were  50  injections  in  all,  but  no  untoward  results 
other  than  a  little  soreness  that  always  follows  hypodermic  injections. 
Seven  patients  received  six  injections  each  and  one  received  eight. — 
/.  Am.  M.  Assoc.,  1913,  v.  61,  p.  2303. 

Rabies  and  the  Pasteur  Treatment. — Anon.  The  work  of 
Pasteur  drew  the  attention  of  the  medical  profession  and  the  laity 
to  rabies,  which  up  to  that  time  had  apparently  been  neglected.  The 
fatality  among  Pasteur-treated  patients  is  less  than  1  per  cent.,  while 
the  death-rate  for  all  persons  bitten  by  rabid  animals  is  considered 
to  be  from  15  to  20  per  cent. — /.  Am.  M.  Assoc.,  1913,  v.  61,  p.  1923. 

Radium. — A  recent  census  of  the  quantity  of  radium  salts  at  pres- 
ent in  the  various  laboratories  of  the  world  shows  that  this  does  not 
exceed  the  equivalent  of  7  gms.  of  metallic  radium.  From  1899  to 
1904,  from  13  tons  of  pitch-blende  residuum,  it  was  possible  to 
extract  only  2  or  3  gms.  of  radium.  Then  a  stop  was  put  by  law 
to  the  export  of  radiferous  material  from  Austria.  Radium  has 
since  been  extracted  in  France  from  much  poorer  ores  containing 
only  from  y2  to  2  mgms.  per  ton,  whereas  the  Austrian  pitch-blende 
contained  quite  100  times  as  much.  Besides  its  use  in  medicine,  its 
application  in  the  industries  is  spreading.  Radium  has  been  used  in 
silk  factories  for  de-electrifying  the  material  and  the  machines.  It 
is  possible  to  realize,  with  radium,  an  apparatus  for  measuring  from 
a  distance  the  potential  of  a  conductor,  without  contact. — Pharm.  J., 
1913,  v.  91,  p.  938. 

Radium  in  Australia. — Anon.  Important  radio-active  minerals 
are  stated  to  have  been  discovered  at  two  places  in  South  Australia. 
In  one  of  these  cases  the  material  as  a  whole  did  not  contain  sufficient 
uranium  and  vanadium  to  be  of  commercial  importance  in  the  crude 
state,  but  results  of  considerable  scientific  interest  are  said  to  have 
been  obtained  in  the  course  of  the  inquiry.  The  composition  of  an- 
other radio-active  ore  in  South  Australia  has  also  been  determined. — 
Pharm.  J.,  1914,  v.  92,  p.  115. 

Saffron. — Holmes,  E.  M.,  in  a  review  of  the  varieties  of  saf- 
fron, points  out  that  although  this  plant  is  cultivated  in  most  of  the 
large  countries  for  home  use,  it  is  exported  from  very  few  and  its 
adulteration  from  the  time  of  Pliny  to  the  present  day  expresses 


140 


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|     March,  1914. 


to  some  extent  its  scarcity.  For  more  than  iooo  and  probably  2000 
years  saffron  has  held  its  own  as  a  medicine  and  as  an  ingredient  in 
food,  and  it  is  hardly  to  be  supposed  that  this  would  be  the  case  if  it 
possessed  no  useful  properties. — Pharm.  J.,  1913,  v.  91,  pp.  941-943. 

Salvarsan. — Editorial.  In  salvarsan  and  neosalvarsan  reliance 
is  placed  in  combinations  of  arsenic  of  complex  molecular  structure. 
In  this  form  the  arsenic  is  relatively  non-toxic,  but  as  in  the  case 
of  many  other  compounds,  the  biochemical  agencies  of  the  body  may 
split  the  complex  chemical  structures  into  simpler  ones,  reducing 
the  non-toxic  combinations  into  products  which  may  be  highly  toxic 
to  the  tissues  of  the  human  organism.  So  long  as  we  are  not  able 
to  predict  with  certainty  what  chemical  reactions  may  take  place 
within  the  body  under  various  conditions,  there  will  remain  more  or 
less  risk  connected  with  the  administration  of  drugs  so  potentially 
toxic  as  are  these  higher  compounds  of  arsenic.  For  future  guid- 
ance, all  instances  of  unfavorable  outcome  after  their  use  should  be 
recorded  in  detail  with  great  care. — /.  Am.  M.  Assoc.,  1913,  v.  61, 
p.  2074. 

Permanent  Scopolamine  Solution. — The  presence  of  the 
higher  alcohols,  such  as  mannitol  or  dulcitol,  in  solutions  of  scopola- 
mine, renders  them  more  permanent,  and  the  use  of  these  for  this 
purpose  is  the  subject  of  a  German  patent. — Pharm.  J.,  1913,  v.  91, 
P-  943- 

Siam  Benzoin. — Holmes,  E.  M.,  gives  an  interesting  summary 
of  the  efforts  that  have  been  made  in  the  last  50  or  60  years  to  find 
the  botanical  source  of  Siam  Benzoin.  The  evidence  adduced  seems 
to  indicate  that  the  chief,  if  not  the  only  source  of  the  Siam  Benzoin 
of  commerce,  is  Styrax  Tonkinense,  Craib,  which  is  found  in  the 
district  between  Luang  Prabang  and  Hanoi ;  second,  that  the  Styrax 
benzoides  of  Northwest  Siam  yield  a  fragrant  resin,  used  locally, 
but  the  evidence  that  it  yields  any  of  the  Siam  benzoin  of  commerce 
is  not  equally  satisfactory. — Pharm.  J.,  1913,  v.  91,  pp.  804-806. 

Spirit  of  Nitrous  Ether. — Hodgson  and  Bailey  report  tests 
to  determine  how  far  the  defense  usually  set  up  in  prosecutions  is 
justified.  Results  show  that  spirit  of  nitrous  ether  retains  its 
strength  remarkably  well  if  kept  in  small,  tightly  stoppered  bottles 
and  not  opened  too  frequently. — Pharm.  J.,  1914,  v.  92,  p.  28. 

Syrups,  Fermentation  of. — Cochran  and  Perkins  report  an  in- 
vestigation on  the  influence  of  small  amounts  of  ethyl  alcohol  on  fer- 
mentation in  cane  sugar  syrup,  and  conclude : 


Am.  Jour.  Pharm.  ) 
March,  1914.  / 


Progress  in  Pharmacy. 


1.  One  per  cent,  or  less  of  alcohol  markedly  accelerates  fermen- 
tation in  syrup  of  average  densities. 

2.  1.25  per  cent,  alcohol  has  very  little  influence. 

3.  Beginning  with  1.25  per  cent,  the  presence  of  alcohol  retards 
fermentation  in  these  syrups,  the  amount  of  retardation  increasing 
with  the  increase  in  the  percentage  of  alcohol. — /.  Ind.  and  Eng. 
Chem.,  1914,  v.  6,  p.  141. 

•  Theoform. — A  condensation  product  of  theobromine  with  a  for- 
maldehyde-liberating substance  has  been  put  on  the  market  under  the 
name  of  theoform.  It  is  claimed  to  contain  85  per  cent,  of  theobro- 
mine, and  is  therefore  richer  in  that  base  than  diuretin  or  agurin.  A 
white,  bitter  powder,  soluble  1 :  50  in  water  at  ordinary  temperatures, 
but  is  not  stable  in  neutral  or  alkaline  solution. — Pharm.  /.,  1914, 
v.  92,  p.  62. 

Thymolphthalein  occurs  in  colorless  needles,  melting  at  245- 
2460  C. ;  readily  soluble  in  alcohol  and  in  acetone ;  sparingly  dissolved 
by  chloroform  or  by  ether.  It  dissolves  in  caustic  alkalies  with  the 
formation  of  a  blue  color;  it  may  therefore  serve  as  an  indicator  for 
alkalimetry,  for  the  color  is  not  affected  by  excess  of  alkali. — 
Pharm.      1913,  v.  91,  p.  881. 

Thyroideum  Siccum. — Bennett,  Reginald  R.,  discusses  the  rela- 
tive weight  of  dried  and  of  fresh  thyroid  gland,  and  questions  the 
frequently  made  statement  that  1  part  by  weight  of  the  dried  thyroid 
represents  5  parts  by  weight  of  the  fresh  thyroid.  Some  observa- 
tions of  his  own  lead  him  to  believe  that  the  relation  is  more  nearly 
1  to  4. — Pharm.  J.,  191 3,  v.  91,  p.  804. 

Tyrene. — Para-iodo-ortho-sulpho-cyclo-hexa-triene  pyridine  is 
conveniently  shortened  for  ordinary  purposes  to  tryene.  An  odor- 
less, non-toxic  powder,  soluble  in  hot  water,  it  is  introduced  as  an 
antiseptic.  Specially  recommended  for  use  in  gynaecology  and  as  a 
dressing  for  wounds,  either  as  a  dusting  powder,  gauze  or  on  tam- 
pons.— Phanm.  J.,  1914,  v.  92,  p.  62. 

Ulsanin. — Described  as  "  hydroiodoborate,"  is  put  forward  as 
a  new  non-poisonous  but  active  disinfectant  and  healing  application 
for  the  treatment  of  wounds.  It  is  a  somewhat  hygroscopic  powder, 
which,  in  contact  with  wound  secretions,  liberates  iodine  and  oxygen. 
— Pharm.  J.,  1913,  v.  92,  p.  102. 

Vaccine. — Anon.  The  virus  of  variola  and  of  vaccinia  is  less 
sensitive  to  the  action  of  glycerin  than  bacteria  in  general,  and  for 
this  reason  it  is  possible  to  obtain  an  almost  pure  virus  of  practically 


142 


Book  Review. 


f  Am.  Jour.  Pharm. 
\      March,  1914. 


full  strength.  Prolonged  action  of  the  glycerin,  however,  destroys 
the  virus,  but  more  rapidly  at  37 0  C.  than  in  the  cold ;  if  kept  at  from 
— 5°  to  — 150  C.  glycerinated  virus  may  remain  active  for  five  years. 
— /.  Am.  M.  Assoc.,  1913,  v.  61,  p.  2074. 

"  Zymase  "  in  Fermentation  Tests. — Rosenbloom,  Jacob.  The 
zymase  of  yeast  can  readily  be  separated  by  grinding  compressed 
yeast  in  a  mortar  with  water  and  sand  and  adding  the  expressed  liquid 
to  5  times  its  volume  of  alcohol.  The  precipitate  is  allowed  to  settle, 
filtered  and  washed  with  alcohol  followed  by  ether.  The  precipitate 
is  then  dried  and  preserved  in  tightly  corked  amber  bottles.  Enzyme 
in  this  form  is  still  active  five  months  after  its  preparation. — /.  Am. 
M.  Assoc.,  1914,  v.  62,  p.  377. 


BOOK  REVIEW. 

E.  Merck's  Annual  Report  of  Recent  Advances  in  Pharma- 
ceutical Chemistry  and  Therapeutics.   1912.   Volume  xxvi. 

It  is  not  only  a  pleasure,  but  pleasure  combined  with  profit  to 
read  this  annual  report  devoted  to  pharmaceutical  chemistry  and 
therapeutics;  profitable  because  it  keeps  one  in  touch  with  current 
literature,  and  particularly  literature  from  foreign  sources,  that  em- 
braces these  two  branches  of  pharmacy  and  medicine.  This  is  clearly 
evidenced  in  the  first  article  which  in  quite  an  exhaustive  manner 
deals  with  Lecithin,  50  pages  being  required  to  deal  with  this  organic 
compound  which  is  so  widely  distributed  in  the  human  and  animal 
organisms,  and  21  pages  containing  references  to  the  literature  con- 
sulted, making  a  total  of  71  pages. 

Preparations  and  drugs  mainly  chemicals,  and  more  particularly 
the  action  of  synthetic  chemicals,  are  commented  upon  as  to  their 
advantages  and  disadvantages  when  introduced  into  the  human 
economy.  When  attention  is  called  to  the  fact  that  this  information 
requires  401  pages  one  can  readily  perceive  what  a  wide  field  is 
covered. 

Organotherapeutics  is  covered  very  thoroughly  and  many  in- 
teresting things  are  brought  to  light  in  connection  with  this  form  of 
medication. 

A  supplement  to  the  report  contains  a  very  informative  paper  by 
Professor  Dr.  R.  Heinz,  Director  of  the  Pharmacological  Institute 
of  the  University  of  Erlangen  on  "  The  Assay  and  Standardisation 
of  Digitalis  Preparations."  j0HN  K  Thum 


Am.  Jour.  Pharm.  ) 
March,  1914.  / 


Current  Literature. 


143 


CURRENT  LITERATURE. 

The  Bad  Taste  in  Hypochlorite-treated  Water-supplies. — 
It  is  surprising,  as  pointed  out  by  Lederer  (Proc.  III.  W ater  Supply 
Assn.,  1913,  p.  235),  that  so  little  attention  has  been  paid  to  the 
question  of  removing  the  taste  from  water-supplies  treated  with 
chlorinated  lime.  In  this  country,  especially,  where  the  treatment 
of  many  large  public  supplies  has  been  carried  out  with  brilliant 
sanitary  success,  there  has  been  frequent  and  often  bitter  complaint 
about  the  taste  of  the  treated  water.  As  well  known,  antagonism  has 
developed  in  many  places  between  water  boards  and  health  depart- 
ments as  a  result  of  these  conditions.  On  one  side  is  the  recognition 
that  the  danger  from  water-borne  diseases  is  greatly  reduced  by 
hypochlorite  treatment:  on  the  other  is  the  necessity  of  having  to 
bear  the  burden  of  daily  complaint  and  to  meet  the  indignant  protests 
of  thousands  of  aggrieved  water-drinkers.  As  pointed  out  by 
Lederer,  a  simple  method  is  available  for  removing  the  taste  from 
hypochlorite-treated  water.  After  careful  experimenting  he  has 
confirmed  the  advantage  of  sodium  thiosulphite  (Na2S203,  5H20)  as 
recommended  by  Bruns.  The  reaction  on  the  residual  chlorin  is  as 
follows :  Na2S203+  8C1  +  5ILO  =  Na2S04+  H2S04+  8HC1.  The 
acids  formed  in  the  neutralization  process  immediately  combine  with 
bases  to  form  neutral  salts.  Lederer  has  obtained  good  results  in  the 
elimination  of  taste  in  Lake  Michigan  water  treated  in  this  way. 
Sodium  thiosulphate  seems  to  possess  -  marked  advantages  over 
sodium  sulphite.  It  must  be  remembered  that  the  action  of  the 
thiosulphate  stops  the  germicidal  action  of  the  chlorin  so  that  it  is 
necessary  to  allow  the  chlorin  to  act  for  a  sufficient  length  of  time 
(Lederer  recommends  from  at  least  ten  to  fifteen  minutes)  before 
the  thiosulphate  is  added.  An  interesting  point  brought  out  in  the 
discussion  of  Lederer's  paper  is  that  hypochlorite  seems  under 
some  conditions  to  accentuate  an  unpleasant  taste  originally 
present  in  the  water.  In  Toledo,  for  instance,  it  is  stated  that  the 
water  develops  a  disagreeable  taste  when  the  river  first  freezes  over, 
owing  to  the  presence  of  large  amounts  of  vegetable  matter  in  the 
water.  The  bad  taste  is  said  to  be  increased  by  even  small  amounts 
of  hypochlorite. — Jour.  A.  M.  A.,  vol.  lxi,  No.  16,  October  18,  1913, 
p.  1464. 


144 


Current  Literature. 


{Am.  Jour.  Pharm. 
March,  1914. 


Studies  in  Carbohydrates,  The  Composition  and  Digesti- 
bility of  Wheat  Bread  and  Allied  Foods,  Gelatinization  of 
Starches. — In  this  paper,  by  Charles  H.  LaWall,  Ph.M.,  and  Sara 
Graves,  B.A.,  published  in  Part  2  of  the  Transactions  of  the  Wagner 
Free  Institute  of  Science  of  Philadelphia,  are  given  tabulated  observa- 
tions of  the  microscopical  characteristics  of  the  following  starches : 
Potato,  Maranta,  Sago,  Tapioca,  Sweet  Potato,  Corn,  Wheat,  Buck- 
wheat, Oat,  Rice,  Barley,  Pea  and  Bean  in  the  raw  state  and  after 
having  been  heated  in  water  to  370,  8o°,  and  ioo°  C.  respectively, 
and  also  after  having  been  subjected  to  these  several  temperatures 
for  a  period  of  30  minutes.  Gelatinization  points  for  the  various 
free  starches  as  well  as  in  pastes  made  from  the  crushed  materials 
would  indicate  that  in  the  crushed  material  the  gelatinization  points 
are  slightly  higher. 

Microscopic  studies  of  the  starch  as  found  in  bread  and  crackers, 
notably  in  Acme,  Freihofer,  Sharpless,  and  Jones  breads  and  in 
Exton,  Sunshine,  Educator  and  Uneeda  Crackers,  Rolls,  Pretzels, 
and  Matzoth  are  tabulated. 

Comparisons  of  the  analyses  of  the  several  breads  and'  crackers 
as  given  would  indicate  but  very  slight  differences  in  these  products. 

From  a  comparison  of  the  ten  tables  included  in  this  paper  it  is 
apparent  that  the  food  values  of  the  various  makes  of  bread  and 
crackers  vary  only  within  very  narrow  limits  and  that  these  varia- 
tions are  largely  due  to  temperature  differences. 

Philip  F.  Fackenthall. 

Pleads  for  Drug  Users. — A  plea  for  the  relief  of  drug  victims 
was  made  by  Dr.  Charles  A.  Towns,  of  New  York,  at  a  legislative 
hearing  in  the  New  York  Legislature  at  Albany  on  February  25,  on 
bills  designed  to  restrict  the  sale  of  habit- forming  drugs,  principally 
cocaine  and  its  derivatives.  A  feature  of  the  proposed  laws  is  a  pro- 
vision designed  to  treat  those  who  obtain  drugs  in  violation  of  the  law 
as  victims  of  disease  and  not  as  criminals.  This  provision  would  give 
a  magistrate  authority  to  commit  habitual  users  of  drugs  to  hospitals 
or  sanatoriums  instead  of  prison. 


THE  AMEBIC  AN 


JOURNAL.  OF  PHARMACY 


The  micro-crystalline  active  principle  of  the  suprarenal  glands, 
Adrenalin,  is  quite  stable  when  chemically  pure.  Since  it  is  a  pure 
principle  with  a  definite  chemical  formula  1  the  powder  does  not 
readily  decompose  when  kept  under  ordinary  conditions.  However, 
because  of  its  comparative  insolubility  in  water  and  its  great  physio- 
logical activity,  the  preparation  most  suitable  for  therapeutic  use 
is  a  i  in  iooo  solution  of  Adrenalin  Chloride,  which  is  an  addition 
product  formed  by  the  action  of  dilute  hydrochloric  acid  upon 
Adrenalin.  In  dilute  solutions  such  as  this,  the  Adrenalin  Chloride  is 
readily  oxidized,  if  no  preservative  is  added  to  the  solution  and  it 
is  exposed  to  the  air.  The  oxidation  and  consequently  the  deteriora- 
tion of  the  solution  is  recognized  by  the  fact  that  the  solution  becomes 
pink,  then  red  and  finally  brown  in  color. 

Due  to  this  tendency  to  deteriorate  by  oxidation,  it  is  claimed 
that  a  dilute  solution  of  Adrenalin  such  as  a  I  in  iooo  solution  would 
not  withstand  sterilization  by  boiling  since  the  heat  would  naturally 
tend  to  hasten  the  oxidation  greatly.  The  solution  is  sterile  when 
put  on  the  market,  but  many  physicians  wish  to  make  doubly  sure 
by  sterilization  immediately  before  use. 

The  following  experiments  were  carried  out  with  the  intention 
of  determining  first,  how  many  times  a  solution  of  Adrenalin  Chlo- 
ride may  be  sterilized  in  a  variety  of  ways  without  deterioration, 
and  second,  the  relative  stability  of  such  a  solution  compared  with 
that  of  a  solution  of  a  synthetic  product.  The  latter,  with  analogous 
properties  and  identical  composition,  is  claimed  2  to  be  more  stable 
than  Adrenalin  which  is  obtained  from  the  suprarenal  glands. 

(i45) 


146  Sterilisation  of  Adrenalin  Solutions.  {AmXp?1?|r'i9ih4arm' 

First  Series. 

In  the  first  experiment  12  ampoules  of  Adrenalin  Chloride  Solu- 
tion 1  in  10,000  were  used.  The  method  of  standardization  of  the 
solutions  which  was  used  in  this  as  well  as  in  all  the  following  ex- 
periments was  the  blood  pressure  method  3  in  which  the  solution  to 
be  tested  is  diluted  till  the  Adrenalin  Chloride  content  is  1  in  100,000. 
This  dilution  is  then  tested  in  comparison  with  a  1  in  100,000  solu- 
tion which  is  made  up  from  an  accurately  weighed  amount  of  C.  P. 
Adrenalin  crystals.  One  ampoule  in  this  series  was  used  as  a 
control  and  its  activity  found  to  be  equal  to  standard.  The  other 
eleven  were  placed  in  boiling  water,  one  ampoule  being  removed 
at  the  end  of  each  15  minutes  and  tested.  Each  was  found  to  be  of 
standard  activity. 

This  experiment  serves  to  show  that  the  activity  of  Adrenalin 
Chloride  Solution  in  ampoules  is  not  impaired  by  sterilizing  in  boil- 
ing water  for  any  period  of  time  up  to  3  hours. 

Second  Series. 

A  second  lot  of  ampoules  of  Adrenalin  Chloride  Solution  was 
used,  one  ampoule  as  before  being  reserved  as  a  control.  The 
others  were  sterilized  for  periods  of  15  minutes  each  and  one  was 
removed  and  tested  after  each  sterilization. 

The  ampoules  for  further  sterilization  were  cooled  to  room  tem- 
perature before  being  sterilized  again  and  the  process  was  not 
repeated  oftener  than  twice  a  day  so  that  considerable  time  elapsed 
between  two  sterilizations. 

Results  were  as  follows : 


Ampoule.  Sterilized.  Activity. 

No.  i  Not  sterilized  Standard 

No.  2  Once  (15  min.)  Standard 

No.  3  Twice  Standard 

No.  4  3    times  Standard 

No.  5  4    times  Standard 

No.  6  5    times  Standard 

No.  7  6    times  Standard 

No.  8  7    times  Standard 

No.  9  8    times  90  per  cent. 

No.  10  9   times  80  per  cent. 

No.  11  10  times  80  per  cent. 

No.  12  11  times  80  per  cent. 


AmApriir'i9u rm' }    Sterilisation  of  Adrenalin  Solutions.  147 

These  results  show  that  ampoules  of  Adrenalin  Chloride  Solu- 
tion can  be  sterilized  a  number  of  times  (in  this  series  7  times) 
without  any  deterioration,  and  after  that  the  loss  of  activity  is 
gradual. 

Third  Series. 

The  next  experiments  give  a  comparison  of  the  stability  of 
Adrenalin  Chloride  Solution  1  in  1000  with  that  of  an  analogous 
synthetic  substance  of  equal  physiologic  activity.  The  latter  was 
made  by  treating  the  crystals  with  dilute  hydrochloric  acid  and 
diluting  1  in  1000.  The  Adrenalin  Chloride  Solution  used  was  made 
from  C.  P.  Adrenalin  crystals  and  contained  no  preservative  other 
than  a  slight  excess  of  hydrochloric  acid.  This  solution  was  tested 
and  found  to  possess  standard  activity. 

Three  different  procedures  were  followed  in  sterilizing  the 
solutions  but  the  conditions  were  duplicated  for  each  solution  in 
order  to  obtain  a  direct  comparison.  The  conditions  to  which  the 
solutions  were  subjected  will  be  briefly  stated  and  the  results  placed 
in  the  form  of  a  table  so  as  to  give  a  better  opportunity  for  com- 
parison. 

In  the  first  method  of  this  series  10  c.c.  of  the  1  in  1000  solu- 
tion to  be  sterilized  was  placed  in  a  graduated  cylinder  which  was 
then  plugged  with  cotton,  and  gradually  heated  in  a  water  bath  to 
the  temperature  of  boiling  water.  This  temperature  was  main- 
tained for  15  minutes  and  at  the  end  of  that  time  the  solution  was 
cooled,  made  up  to  its  original  volume  if  any  loss  due  to  evaporation 
had  occurred,  and  one  cubic  centimeter  removed  for  testing.  This 
process  was  repeated  four  times. 

In  the  second  method  25  c.c.  of  the  solution  to  be  sterilized 
was  placed  in  a  tightly  corked  bottle  which  was  then  partially  im- 
mersed in  boiling  water  for  periods  of  15  minutes  each.  Under 
these  conditions  there  was  no  loss  by  evaporation.  Each  solution 
was  submitted  to  four  periods  of  sterilization  and  a  test  of  its 
activity  made  after  each  period. 

In  the  third  method  of  this  series  20  c.c.  of  the  solution  to 
be  tested  was  placed  in  a  small  open  flask  and  boiled  over  a  flame 
for  5  minutes.  After  each  period  of  boiling  the  loss  due  to  evapora- 
tion, which  was  considerable,  was  made  up  with  distilled  water  and 
the  activity  of  the  solution  then  determined. 


148 


Sterilisation  of  Adrenalin  Solutions. 


\  Am.  Jour.  Pharm. 
t      April,  1914. 


The  results  of  the  above  experiments  were  all  checked  and  are 
summarized  in  the  following  table : 


Solution  of  Adrenalin  Chloride. 


Solution  of  Synthetic  Sub- 


First  Method : 

Cotton  plugged  > 

tube  in  boiling  j 

water  15  minutes  j 

at  a  time.  J 

Second  Method  : 
Tightly  stop- 
pered  bottle 
in  boiling  water  [ 
15  minutes  at  a  time.  J 

Third  Method : 
Boiled  5 
minutes  over 
flame  in  open 
flask. 


1st  ster. 
per 


1.  IOO 

2.  IOO 


1.  IOO 

2.  IOO 


1.  IOO 

2.  IOO 


2nd. 
per 


IOO 
IOO 


IOO 
IOO 


IOO 
IOO 


3rd. 
per 


4th. 
per 


1st  ster. 
per 


stance. 
2nd. 
per 


cent.  cent. 


3rd.  4th. 
per  per 
cent.  cent. 


90 
90 


IOO 

90 


90 
IOO 


80 
90 


90 
90 


75 
90 


1.  100     100     80  80 


1.  IOO 

2.  IOO 


1.  IOO 

2.  IOO 


IOO 
90 


90 
90 


70 
80 


80 
80 


70 


75 
80 


The  results  obtained  show  that  Adrenalin  Chloride  Solution  1  in 
1000,  containing  no  preservative  other  than  a  slight  excess  of  hydro- 
chloric acid,  can  be  sterilized  at  least  twice  by  heating  to  the  tem- 
perature of  boiling  water  under  various  conditions  without  losing 
any  activity.  After  this  the  loss  is  quite  gradual,  so  that  it  prob- 
ably would  not  be  noticeable  therapeutically  until  after  the  fourth 
or  fifth  sterilization.  By  a  comparison  of  the  results  obtained -with 
Adrenalin  Chloride  Solution  and  the  solution  of  the  synthetic  sub- 
stance it  can  be  seen  that  the  loss  of  activity  due  to  sterilization 
occurs  more  quickly  in  the  case  of  the  latter  solution  and  also  that 
the  deterioration  is  more  marked. 


Summary. 

1.  Adrenalin  Chloride  Solution  in  ampoules  can  be  heated  con- 
tinuously for  3  hours  to  the  temperature  of  boiling  water  without 
any  loss  of  activity. 

2.  Adrenalin  Chloride  Solution  in  ampoules  can  be  sterilized  by 
immersion  in  boiling  water  for  seven  distinct  periods  of  15  minutes 
each  without  loss  of  activity. 


AmAp?nr'i9ih4rm" }  Solubility  of  Phenol  in  Hydrocarbons.  149 

3.  Adrenalin  Chloride  Solution  can  be  exposed  to  the  air  and 
sterilized  at  least  twice  under  a  variety  of  conditions  without  loss 
of  activity. 

4.  Adrenalin  Chloride  Solution  is  more  stable  than  the  Solution 
of  a  synthetic  compound  when  both  are  subjected  to  the  same  sterili- 
zation treatment.  The  results  obtained  disprove  the  statement  that 
the  stability  of  the  synthetic  exceeds  that  of  the  natural  product. 

REFERENCES. 

1  Aldrich :   Jour.  Amer.  Chem.  Soc,  September,  1905. 

2  Stoll :  Lancet-Clinic,  June  21,  1913. 

3  Houghton:  Jour.  Amer.  Med.  Assoc.,  January  18,  1902. 

From  the  Research  Laboratory  of  Parke,  Davis  &  Co.,  Detroit, 
Michigan. 

NOTE  ON  THE  SOLUBILITY  OF  PHENOL  IN 
HYDROCARBONS. 

By  J.  D.  PlLCHER. 

Pharmacological  Laboratory,  School  of  Medicine,  Western  Reserve 
University,  Cleveland. 

The  Pharmacopoeia  states  that  Phenol  is  very  soluble  in  fixed 
oils.  It  is  less  soluble  in  the  mineral  oils ;  as  determined  in  this 
laboratory  one  gram  of  Phenol  dissolves  in  8-9  c.c.  of  Petroleum, 
20-21  c.c.  Petroleum  benzine,  45-50  c.c.  of  Petrolatum  liquidum. 
It  is  about  twice  as  soluble  in  solid  Petrolatum  (1  in  23-24)  as  in 
the  liquid  petrolatum.  This  difference  in  solubility  of  Phenol  in 
the  vegetable  and  animal  oils  and  in  the  mineral  oils  is  worthy  of 
note  for  two  reasons :  In  removing  Phenol  from  the  skin  after  acci- 
dental application  the  mineral  oils  would  be  less  efficacious  than  the 
fixed  oils,  glycerin  and  alcohol  and  of  little  more  value  than  water. 
However,  when  the  local  "action  is  desired,  ointments  and  liquid 
preparations  of  Phenol  in  the  mineral  oils  would  be  more  active  than 
preparations  containing  the  same  percentage  of  Phenol  in  the  animal 
or  vegetable  oils,  inasmuch  as  the  mineral  oils  would  part  with  the 
Phenol  more  readily  than  the  other  oils. 

Methods. — Weighed  amounts  of  crystallized  Phenol  were  added 
to  the  liquid  hydrocarbons  and  allowed  to  stand,  with  frequent 


Paraffin  Oil. 


(Am.  Jour.  Pharra. 
t      April,  1914. 


shaking,  several  hours  or  over  night.  Small  quantities  of  the  oils 
were  then  added  until  the  Phenol  was  completely  dissolved.  In  dis- 
solving the  Phenol  in  the  petrolatum  the  mixture  was  thoroughly 
stirred  while  heating  to  the  melting  point;  on  cooling,  the  mixture 
was  examined  microscopically  for  Phenol  crystals  and,  when  found, 
the  process  was  repeated  with  the  addition  of  small  amounts  of 
petrolatum  until  no  crystals  were  visible. 


RENEWED  INTEREST  IN  PARAFFIN  OIL.1 
By  M.  I.  Wilbert,  Washington,  D.  C. 

Within  recent  years  renewed  interest  is  being  taken  in  paraffin 
oil  for  internal  administration  in  the  treatment  of  intestinal  stasis 
or  chronic  constipation.  This  renewed  interest  is  largely  due  to  the 
fact  that  a  notable  English  surgeon,  Sir  W.  Arbuthnot  Lane,  in  his 
experimental  work  to  prevent  the  formation  of  adhesions  after  sur- 
gical interference  in  the  intestinal  tract,  found  that  paraffin  oil 
served  as  an  intestinal  lubricant  and  was  of  material  assistance  in 
overcoming  persistent  constipation. 

This  use  of  paraffin  oil  is  by  no  means" new,  however,  and-dates 
back  many  years  to  the  introduction  of  refined  petroleum  products 
by  Cheseb rough  and  others  about  1872. 

Previous  to  this  date  the  residues  in  petroleum  stills  had  little 
or  no  commercial  value  and  were  used  almost  exclusively  as  lubri- 
cants, more  particularly  axle  grease.  The  possibility  of  producing 
an  odorless  and  practically  colorless  oil  and  heavier  fat  by  compara- 
tively simple  methods,  presented  the  peculiar  problem  of  establishing 
a  market  for  products  of  this  kind  and  for  some  years  at  least  the 
substances  were  used  largely,  if  not  exclusively,  for  the  adulteration 
of  other  fats  and  oils,  and  it  is  this  use  of  vaseline  and  of  vaseline 
oil  as  adulterants  that  later  led  to  experiments  to  demonstrate  their 
possible  food  value  and  the  presence  or  absence  of  harmful  or  toxic 
ingredients.  Experiments  carried  on  by  N.  A.  Randolph,  Philadel- 
phia, about  1884,  not  only  demonstrated  that  the  heavier  petroleum 
products  were  not  absorbed  from  the  intestinal  tract  but  also  showed 
that  they  served  to  act  somewhat  in  the  nature  of  foreign  material, 

1  Presented  at  the  meeting  of  the  City  of  Washington  Branch  of  the  A. 
Ph.  A.,  March  18,  1914. 


Am.  Jour.  Pharm.  ) 
April,  1914.  / 


Paraffin  Oil. 


and  might  have  some  value  in  the  treatment  of  certain  forms  of  con- 
stipation. It  was  also  thought  that  these  products  appeared  to  inhibit 
fermentation  and  would,  therefore,  be  of  value  in  the  treatment 
of  certain  forms  of  diarrhoea.  Some  fifteen  years  later,  Robert 
Hutchinson  of  England  reported  practically  the  same  observations 
and  this  report  led  to  the  then  quite  extensive  use  of  petroleum 
and  of  paraffin  oils  for  various  intestinal  disorders. 

The  at  one  time  widespread  use  of  purified  petroleum  products 
in  the  treatment  of  pulmonary  disorders,  is,  to  some  extent,  traceable 
to  the  administration  of  the  naturally  occurring  petroleum  products 
in  various  countries  and  at  various  times.  Crude  petroleum  has  been 
used  from  time  immemorial  as  a  medicine  and  perhaps  largely  be- 
cause of  its  disagreeable  odor  was  from  very  early  times  used  in 
the  treatment  of  diseases  of  the  respiratory  tract.  In  this  country 
"  Seneca  oil  "  had  considerable  vogue  from  time  to  time  and  was 
frequently  put  out  in  the  form  of  proprietary  or  "  patent  prepara- 
tions "  for  the  treatment  of  various  diseases.  After  the  introduction 
of  purified  petroleum  products  these  were  offered  as  substitutes  for 
the  formerly  used  crude  oil  and,  even  at  the  present  time,  the  adver- 
tising matter  put  out  in  connection  with  some  of  the  popularly  ex- 
ploited preparations  of  petroleum  do  not  satisfactorily  designate 
whether  or  no  the  crude  or  the  purified  product  is  being  advocated. 

During  the  past  three  or  four  decades,  purified  petroleum  products 
have  been  marketed  under  scores,  if  not  hundreds,  of  proprietary 
names  and  the  misleading  claims  and  statements  made  in  connection 
with  these  several  preparations  are  far  from  being  a  credit  to  the 
owners  or  to  the  persons  who  act  as  distributers  for  the  several 
articles.  That  there  is  some  element  of  truth  in  the  claims  that  have 
been  made  for  petroleum  products  is  evidenced  by  the  fact  that  the 
use  of  petroleum,  crude  and  refined,  has  persisted  in  all  parts  of  the 
world  and  has  at  times,  like  the  present,  reached  amounts  that  were 
quite  considerable. 

With  the  renewed  interest  in  paraffin  oil  that  is  in  evidence  at 
present,  the  time  appears  to  be  particularly  opportune  for  pharma- 
cists who  are  willing  to  assist  in  making  for  true  progress  to  do 
missionary  work  and  to  point  out  to  physicians  in  a  rational  and 
sensible  way  that  paraffin  oil  and  other  petroleum  products,  while 
they  may  be  useful,  must  have  limitations,  that  many  of  the  claims 
made  for  the  proprietary  articles  are  unfounded  and  not  based  on 
fact,  that  in  the  event  that  the  physician  does  wish  to  experiment 


Paraffin  Oil. 


f  Am.  Jour.  Pharm. 
\      April,  1914. 


with  the  product,  non-proprietary  oils  of  high  quality  are  readily 
available  and,  finally,  that  these  non-proprietary  products  can  be 
sold  to  the  patient  at  a  very  much  lower  figure  than  can  the  pro- 
prietary article  and  still  yield  the  retail  druggist  a  more  satisfactory 
profit. 

As  intimated  above,  the  products  that  are  available  at  the  present 
time  are  many,  or  at  least  appear  to  be  numerous  because  of  the 
varied  trade  names  under  which  they  are  offered.  On  studying  the 
nature  of  these  products,  however,  it  appears  that  there  is  no  very 
great  difficulty  in  establishing  certain,  at  times  perhaps  arbitrary, 
lines  of  demarcation  between  them  and  identifying  them  as  belong- 
ing to  one  or  the  other  class  of  commercially  available  oils  readily 
obtainable  by  any  pharmacist. 

The  bulk  of  the  available  supply  of  heavy  mineral  oil  comes  from 
two  sources  and  the  products  differ  materially  in  chemical  composi- 
tion. The  American  oil  is  obtained  from  paraffin  base  petroleum  and 
consists  essentially  of  hydrocarbons  of  the  methane  series  having  the 
general  formula  CnH2n  -f-  2. 

The  so-called  Russian  Oil,  obtained  largely,  if  not  entirely,  from 
the  oil  wells  in  the  Baku  district,  consists  chiefly  of  monocylic  poly- 
methylenes  or  napthenes,  having  the  general  formula  CnH2n. 
These  latter  products  have  been  described  as  hydrated  aromatic 
hydrocarbons  and  while  they  behave  with  reagents  very  much  in  the 
same  way  as  do  the  hydrocarbons  of  the  methane  series,  they  are 
more  readily  purified  and  generally  occur  in  commerce  as  water 
white  oils  that  are  quite  free  from  fluorescence  or  odor.  The  Amer- 
ican paraffin  or  methane  oils  usually  have  a  distinct  color  and  are 
seldom  quite  free  from  fluorescence  or  a  peculiar  dichroic  effect 
that  is  particularly  noticeable  when  the  preparation  is  viewed  by 
reflected  light.  Apart  from  the  appearance,  however,  there  is  no 
evidence  that  the  two  products  differ  in  their  effect  on  the  animal 
organism  and  one  has  perhaps  as  many  advocates  and  users  as  the 
other. 

The  density  of  the  commercially  available  products  also  varies 
and  the  fact  that  it  is  proposed  to  extend  the  present  U.  S.  P.  limits 
of  specific  gravity,  0.870  to  0.940  at  25  °,  to  read  0.845  to  0.940  at 
25 0  clearly  indicates  that  the  members  of  the  present  Committee  of 
Revision  are  themselves  not  convinced  as  to  the  properties  that 
should  be  inherent  in  a  mineral  oil  for  medicinal  use. 

The  paraffin  oils  official  in  the  Pharmacopoeias  of  the  Continent 


Am.  Jour.  Pharm.  > 
April,  1914.  } 


Paraffin  Oil. 


153 


of  Europe  are  usually  of  the  denser  variety,  0.865  or  higher  at  150, 
but  this  is  probably  due  to  the  fact  that  there  the  oil  is  largely  used 
as  a  basis  for  ointments  and  the  various  other  uses  are  only  now 
being  developed. 

In  this  country  paraffin  oil  or$  as  it  is  better  known,  liquid  petro- 
leum, has  long  been  in  use  as  a  basis  for  oil  sprays  in  the  treatment 
of  affections  of  the  nose  and  throat  and  for  this  purpose  the  lighter 
and  more  limpid  oil  appears  to  be  preferred.  For  internal  adminis- 
tration Sir  W.  Arbuthnot  Lane  prefers  the  heavier,  European  type 
of  oil  and  this  is  now  available  in  this  country  and  is  being  intro- 
duced by  a  number  of  manufacturers  and  dealers  under  proprietary 
titles,  to  be  sold  at  fancy  prices.  Even  for  internal  use,  however, 
there  appears  to  be  a  definite  limit  to  the  solid  paraffin  that  an  oil 
can  hold  in  solution  and  be  palatable  or  readily  taken.  At  compara- 
tively low  temperatures  some  of  these  oils  are  nearly  solid  and  even 
at  ordinary  temperatures  they  are  so  viscid  that  they  do  not  readily 
leave  the  mouth  when  taken  internally. 

Up  to  the  present  time  it  is  by  no  means  positively  established 
that  the  comparatively  dense  or  the  viscid  oil  is  to  be  uniformly  pre- 
ferred for  internal  administration,  and  the  pharmacist  can  be  of 
service  not  alone  in  assisting  the  physician  to  determine  which  of 
the  two  products  is  the  preferable  one  but  also  in  devising  methods 
of  administration  and  preferable  flavors  to  overcome  the  objection- 
able taste  of  the  oil,  particularly  of  the  denser  variety  of  oil. 

One  further  question  that  may  be  discussed  briefly  is  the  dose. 
One  firm,  the  owner  of  the  product  most  widely  used  in  this  coun- 
try, says : 

"  Excellent  results  are  obtained  by  giving  the  oil  in  small  doses. 
In  mild  cases  a  tablespoonful  at  night  gives  prompt  relief.  In  longer 
standing  cases  make  it  almost  a  part  of  the  diet  and  give  one  or  two 
teaspoonfuls  just  after  meals." 

Dr.  Lane  and  many  of  his  followers,  on  the  other  hand,  give  the 
oil  in  much  larger  doses  and  insist  that  it  be  given  shortly  before 
meals  so  as  not  to  interfere  in  any  way  with  the  digestion  of  food 
which  it  probably  would  if,  as  proposed  above,  it  were  given  with  or 
immediately  after  meals  and  thereby  intimately  mixed  with  the 
stomach  content. 

Bastedo,  in  his  book  on  materia  medica,  pharmacology,  thera- 
peutics and  prescription  writing,  states  that  the  oil  is  only  mildly 
laxative  and  should  be  given  in  doses  of  30  c.c.  two  or  three  times 


154 


Paraffin  Oil. 


Am.  Jour.  Pharm. 
April,  1914. 


a  day.  Other  authorities  advise  even  larger  doses,  and  Robinson 
(Medical  News,  1900,  v.  77,  p.  56)  reports  that  he  frequently  admin- 
istered nearly  a  pint  in  a  few  hours  without  any  indications  of  dis- 
comfort and  no  untoward  results  of  any  kind.  Robinson  also  asserts 
that  he  was  able  to  duplicate  the  experiments  reported  by  Randolph 
and  reclaim  all  of  the  oil  that  was  ingested.  Some  recent  German 
experimenters,  however,  appear  to  believe  that  a  part,  at  least,  of 
the  oil  is  changed  or  absorbed  in  the  intestinal  tract,  and  while  the 
bulk  of  it  passes  through  unchanged  it  is  not  possible  to  reclaim 
absolutely  all  of  the  oil  as  taken.  At  the  present  time,  the  preferred 
dose  is  from  one  to  two  tablespoonfuls  one  hour  before  meals, 
or  from  two  to  four  tablespoonfuls  on  retiring.  The  oil  may  be 
flavored  to  make  it  less  objectionable,  and  several  authorities  appear 
to  prefer  administering  the  product  in  the  form  of  an  emulsion, 
though  others  claim  that  the  emulsion  is  not  so  satisfactory  and 
does  not  give  the  same  uniform  good  results. 

In  addition  to  its  use  internally  as  a  lubricant  or  laxative,  paraffin 
oil  is  also  given  in  the  form  of  rectal  injections,  and  is  being  ex- 
ploited more  recently  as  a  dressing  for  wounds,  both  recent  and 
chronic.  In  connection  with  chronic  ulcers  it  is  being  extolled  as  a 
dressing  to  protect  the  skin  around  the  focus  of  suppuration.  The 
oil  in  these  cases  not  alone  protects  the  skin  against  irritation  from 
oozing,  thus  warding  off  eczema,  but  also  keeps  the  dressings  from 
sticking. 

The  use  of  liquid  petroleum  as  a  soothing  application  in  the  form 
of  a  spray  to  inflamed  mucous  membranes  of  the.  nose  and  throat 
is  well-known,  as  is  the  use  of  the  same  product  in  cosmetics,  such 
as  skin  creams  or  pomades,  and  the  use  of  this  product  for  these 
several  purposes  need  not  be  discussed  at  this  time. 

In  conclusion,  then,  the  object  of  this  communication  is  to  call 
attention  to  the  renewed  interest  that  is  being  manifested  by  medical 
men  in  paraffin  oil  for  internal  administration,  and  as  an  adjuvant 
dressing  for wounds,  and  to  suggest  to  pharmacists  that  they  ac- 
quaint themselves  with  the  properties  of  the  available  material  for 
the  purpose  of  pointing  out  to  physicians  the  nature  and  the  kind  of 
material  that  is  available  as  well  as  the  limitations  that  probably 
exist. 


^mAp°r?Ci9Hrm'}  United  States  Public  Health  Service.  155 


THE  UNITED  STATES  PUBLIC  HEALTH  SERVICE.1 


By  John  F.  Anderson,  Director  Hygienic  Laboratory,  U.  S.  Public  Health 
Service,  Washington,  D.  C. 

The  Federal  Public  Health  Service  is  a  bureau  of  the  Treasury 
Department.  Beginning-  as  the  Marine  Hospital  Service,  through 
successive  acts  of  Congress  it  has  undergone  a  process  of  evolution 
so  that  all  of  its  duties  are  essentially  of  a  public  health  character, 
and  it  is  organized  with  a  view  to  their  performance. 

The  central  bureau  at  Washington,  which  is  presided  over  by 
the  surgeon-general,  has  seven  divisions,  as  follows : 

1.  Personnel  and  accounts. 

2.  Foreign  and  insular  quarantine  and  immigration. 

3.  Domestic  (interstate)  quarantine  and  sanitation. 

4.  Sanitary  reports  and  statistics. 

5.  Scientific  research. 

6.  Marine  hospitals  and  relief. 

7.  Miscellaneous. 

Each  of  the  six  divisions  first  mentioned  is  in  charge  of  an 
assistant  surgeon-general,  who  is  directly  responsible  for  administra- 
tive matters  in  connection  with  his  division.  The  officer  who'  has 
charge  of  the  Division  of  Personnel  and  Accounts  has  immediate 
supervision  of  the  entire  personnel  and  appropriations,  and  the 
preparation  of  the  annual  estimates  therefor. 

Through  the  Division  of  Foreign  and  Insular  Quarantine  and 
Immigration  are  administered  all  matters  relating  to  maritime  quar- 
antine and  medical  inspections  of  aliens. 

Through  the  Division  of  Interstate  Quarantine  are  administered 
all  matters  relating  to  the  control  of  contagious  and  infectious  dis- 
eases in  interstate  traffic. 

The  Division  of  Sanitary  Reports  and  Statistics  handles  all 
matters  relating  to  the  collection  of  morbidity  reports,  reports  of 
epidemics,  and  of  information  pertaining  to  the  geographic  distri- 
bution of  disease  and  to  climate  in  relation  to>  health  and  disease. 

The  Division  of  Scientific  Research  administers  all  matters  re- 
lating to*  investigations  of  contagious  and  infectious  diseases  and 

1  Abstract  of  a  lecture  delivered  by  invitation  March  9,  1914,  before  the 
Philadelphia  College  of  Pharmacy. 


156  United  States  Public  Health  Service.  {Am•A^•1p^Jf^• 

matters  pertaining  to  the  public  health  wherever  made.  In  the  field 
it  is  represented  by  the  Hygienic  Laboratory  with  its  four  divisions, 
the  plague  laboratory  in  San  Francisco,  the  leprosy  investigation 
station  in  Hawaii,  the  pellagra  investigation  station  at  Savannah, 
Ga.,  the  station  at  Wilmington,  N.  C,  for  the  investigation  of  the 
parasites  of  man,  and  by  officers  engaged  in  investigations  of  typhoid 
fever,  Rocky  Mountain  spotted  fever,  poliomyelitis,  etc.,  in  dif- 
ferent parts  of  the  country,  and  sanitary  surveys  of  navigable  waters 
wherever  conducted. 

In  the  Division  of  Marine  Hospitals  and  Relief  are  administered 
all  matters  connected  with  the  care  and  treatment  of  seamen  and 
recruiting  for  the  several  bureaus  of  the  department. 

To-day  the  Public  Health  Service  has  a  corps  of  approximately 
450  medical  officers,  50  pharmacists,  and  a  total  personnel  of 
about  2,000. 

In  the  public  health  law  of  July  1,  1902,  provision  is  made  for 
annual  conferences  between  the  Public  Health  Sendee  and  state 
boards  and  departments  of  health.  Provision  is  also  made  for  special 
conferences  with  all  or  a  part  of  the  state  health  organizations,  and 
upon  the  application  of  not  less  than  five  state  health  authorities,  a 
special  conference  must  be  called.  In  effect,  there  is  thus  provided 
an  advisory  council  on  administrative  matters,  which  in  its  devel- 
opment will  insure  cooperation  and  be  an  arbiter  on  vexed  sanitary 
questions,  and  in  which  each  state  is  entitled  to  representation. 

In  the  same  law  Congress  also  provided  for  an  advisory  board 
for  consultation  relative  to  investigations  to  be  inaugurated  and 
the  methods  of  making  them  in  the  Hygienic  Laboratory.  By  this 
means  the  service  is  brought  in  touch  with  the  great  scientific  labora- 
tories, and  may  avail  itself  of  advice  from  the  highest  sources. 

Congress  has  thus  made  provision  for  councils  in  respect  to  both 
administrative  and  scientific  matters.  Their  utilization  in  the  highest 
degree  is  one  of  the  most  important  means  of  development  of  public- 
health  organization  and  public-health  work. 

The  necessity  for  more  ana1  more  extensive  Federal  supervision 
over  international  traffic  was  made  apparent  by  repeated  epidemics. 
The  first  permanent  quarantine  law,  passed  April  29,  1878,  was  a 
result  of  the  widespread  and  severe  epidemic  of  yellow  fever  during 
the  previous  year.  The  passage  of  the  law  of  February  15,  1893, 
was  intimately  associated  with  the  outbreak  of  cholera  in  Europe  in 
1892,  and  the  quarantine  act  of  June  19,  1906,  followed  the  epidemic 


m'Av£*; ml™'}  United  States  Public  Health  Service.  157 

of  yellow  fever  in  the  Southern  States  in  1905.  Under  the  above- 
mentioned  laws  and  a  few  minor  ones,  there  was  finally  developed 
the  national  system  of  quarantine  as  it  exists  to-day — a  system,  the 
development  of  which  occupied  approximately  100  years. 

All  quarantine  operations  in  the  United  States  are  conducted 
under  the  supervision  of  the  Federal  Government,  and,  with  two  or 
three  exceptions,  all  stations  are  conducted  by  Federal  officers. 

A  long  series  of  immigration  laws  have  been  enacted  between 
the  periods  March  20,  1819,  and  February  20,  1907,  their  general 
objects  from  a  hygienic  standpoint  being  the  improvement  of  the 
health  and  comfort  of  arriving  aliens,  and  the  development  of  a 
stronger  race  in  the  United  States. 

On  arrival  at  domestic  ports,  all  aliens  are  required  to  undergo 
medical  inspection,  and  for  those  suffering  with  disease,  hospitals 
are  maintained.  This  medical  inspection  is  conducted  by  the  Public 
Health  Service. 

The  administrative  procedures  in  international  sanitation  having 
been  established,  and  their  further  improvement  assured,  the  great 
public  health  problems  of  the  Nation  are  now  of  an  interstate  and 
intrastate  character. 

The  Federal  public  health  statutes  are  based  upon,  or  are  care- 
fully in  accord  with  that  clause  of  the  Constitution  which  gives  the 
right  to  Congress  to  regulate  commerce  between  the  states.  On 
account  of  the  far-reaching  effect  of  interstate  intercourse  on  our 
national  life,  the  field  for  public  health  activities  on  the  part  of  the 
Federal  Government  is  wide. 

Under  the  quarantine  act  of  February  15,  1893,  the  secretary  of 
the  Treasury  is  authorized  to  issue  regulations  for  the  prevention 
of  the  spread  of  infectious  and  contagious  diseases  from  one  state 
to  another,  where  the  regulations  of  the  states  are  inadequate. 
These  regulations  may  be  enforced  by  state  and  local  authorities, 
but  the  Federal  Public  Health  Service  is  authorized  to  cooperate  in 
their  enforcement,  and  should  the  states  fail  or  refuse,  the  Presi- 
dent may  adopt  such  measures  as  in  his  judgment  shall  be  necessary. 

Examples  of  work  of  this  character  that  may  be  mentioned  are 
cooperative  measures  for  the  collection  and  examination  of  rodents 
to  prevent  plague;  anti-typhoid  campaigns  in  urban  and  rural  dis- 
tricts, and  sanitary  surveys  of  interstate  and  international  waters  in 
relation  to  the  prevention  of  the  spread  of  typhoid  fever. 

There  is  necessity  not  only  of  quarantine  measures  to  prevent  the 


158  United  States  Public  Health  Service.  |  AmipSir'i34  ™* 

spread  of  communicable  diseases,  but  sanitary  measures  to  prevent 
their  propagation.  These  include  the  sanitation  of  trains  and  vessels 
and  the  supplies  used  aboard,  the  regulation  of  conditions  under 
which  the  employees  of  common  carriers  work,  and  the  exclusion  of 
dangerous  or  infected  merchandise  from  transportation. 

On  account  of  the  relation  of  epidemics  to  the  hygienic  and 
commercial  welfare  of  the  country,  the  Federal  Public  Health  Service 
may,  under  the  provisions  of  the  above-mentioned  law,  assume  re- 
sponsibilities in  respect  to  their  control  under  the  direction  of  the 
Secretary  of  the  Treasury  and  the  President.  In  the  event  of  out- 
breaks of  cholera,  yellow  fever,  smallpox,  plague,  or  typhus  fever 
in  any  part  of  the  United  States,  the  President  is  also  authorized  to 
cause  regulations  to  be  issued  and  enforced  to  prevent  their  spread, 
and  an  epidemic  fund  of  approximately  half  a  million  dollars  is 
appropriated  annually  for  expenditures  of  the  Federal  Public  Health 
Service  in  suppressing  epidemics  of  these  diseases. 

It  is  under  such  authority  that  the  epidemics  of  yellow  fever  in 
the  Southern  States,  the  outbreaks  of  plague  in  California  and  our 
island  possessions,  and  similar  outbreaks  have  been  handled. 

Relation  of  the  Public  Health  Service  to  Pharmacy, 

The  reorganization  of  the  Marine-Hospital  Service  in  1871,  under 
the  direction  of  a  supervising  surgeon-general,  materially  broadened 
the  object  and  scope  of  the  service  and  evidenced  the  advisability  of 
extending  the  work  so  as  to  provide  for  much  needed  supervision 
of  varied  interests  relating  to  the  public  health. 

Of  the  many  activities  that  were  early  developed  by  the  service 
in  this  connection,  few  are  of  more  wide-spread  importance  to  the 
welfare  of  the  public  at  large,  or  more  intimately  connected  with 
the  medical  efficiency  of  the  service  itself,  than  the  efficient  control 
of  medicinal  substances  and  active  participation  and  interest  in  the 
revision  of  the  Pharmacopoeia  of  the  United  States.  This  service 
has  been  regularly  represented  at  each  decennial  meeting  of  the 
Pharmacopceial  Revision  Convention  held  since  its  reorganization 
as  a  bureau  in  1871,  and  several  of  the  representatives  of  the  Marine- 
Hospital  Service  have  served  as  members  of  the  revision  committee. 
The  first  of  the  representatives  of  the  service  to  be  elected  to  serve 
as  a  member  of  the  Committee  of  Revision  was  a  pharmacist,  Oscar 
Oldberg,  who  was  the  delegate  of  the  then  U.  S.  Marine-Hospital 


***a.^ST" iSSC™" }  United  States  Public  Health  Service.  159 

Service  to  the  Pharmacopceial  Convention  in  1880.  This  service  was 
also  among  the  first  of  the  government  services  to  adopt  the  phar- 
macopoeia as  the  standard  for  its  medical  supplies  and  to  require 
that  drugs  and  medicines  conform  strictly  with  these  official  require- 
ments. 

In  this  connection  it  may  also*  be  of  interest  to  point  out  that 
this  service  was  the  first  to  systematically  use  the  metric  system  of 
weights  and  measures  and  that  this  use  of  the  metric  system  by  one 
of  the  government  medical  services  played  a  very  important  part  in 
the  practical  adoption  of  the  metric  system  of  weights  and  measures 
in  the  sixth  decennial  revision  of  the  Pharmacopoeia  of  the  United 
States. 

The  use  of  the  metric  system  of  weights  and  measures  was  made 
compulsory  in  the  then  "  Marine-Hospital  Service "  by  an  order 
signed  by  the  Secretary  of  the  Treasury,  John  Sherman,  in  1878,  at 
the  request  of  Prof.  Oldberg,  and  the  steps  that  led  up  to  the  sign- 
ing of  the  order  are  well  foreshadowed  in  the  report  of  the  Super- 
vising General,  John  M.  Woodworth,  on  the  operation  of  the  Marine- 
Hospital  Service  for  the  fiscal  year  1877,  which  includes  a  lengthy 
report  on  the  adoption  of  metric  system  of  weights  and  measures 
for  medical  and  pharmacal  purposes,  by  Oscar  Oldberg,  then  chief 
clerk  and  acting  medical  purveyor  of  the  United  States  Marine- 
Hospital  Service. 

With  the  change  of  name  to  the  Public  Health  Service,  the  need 
for  cooperation  in  improving  the  available  supply  of  remedies  used 
in  the  treatment  of  diseases  and  the  perfecting  of  the  scientific  accu- 
racy in  pharmacopceial  requirements  has  become  more  and  more  ap- 
preciated and  provisions  have  from  time  to  time  been  made  for  active 
cooperation  in  the  work  of  associations  interested  in  the  promulga- 
tion of  the  truth  regarding  the  nature  of  medicines  of  various  kinds. 
The  general  importance  of  this  work  from  a  public  health  point  of 
view  had  in  a  measure  been  foreseen  by  the  inauguration  of  the 
Division  of  Scientific  Research  and  the  establishment  in  the  Hygienic 
Laboratory  of  a  division  of  pharmacology  devoted  to  the  scientific 
investigation  of  drugs  as  they  relate  to  the  public  health,  particu- 
larly as  to  their  potency,  efficiency  and  pharmacopceial  purity.  Also 
and  in  a  more  direct  way,  by  the  authorization  by  law  to  undertake 
the  supervision  and  practical  control  of  certain  important  medicinal 
products,  such  as  sera  and  vaccines. 

In  1902  Congress  passed  a  law  requiring  that  all  persons  or  firms 


160  United  States  Public  Health  Service.  {AmXprSr'i9i4arm* 

engaged  in  the  manufacture  and  interstate  sale  of  viruses,  serums, 
toxins,  and  similar  products  should  be  licensed  by  the  Secretary  of 
the  Treasury  for  the  sale  of  such  products.  An  inspection  has  to  be 
made  of  the  stables,  methods,  etc.,  of  the  firm  desiring  to  be  licensed 
and  an  examination  of  all  their  products  has  to  be  made  in  the 
Hygienic  Laboratory.  After  a  consideration  of  the  inspector's  re- 
port on  the  firm's  plant  and  the  report  on  the  examination  in  the 
Hygienic  Laboratory  of  the  various  products,  a  license  is  either 
issued  or  declined.  In  connection  with  the  enforcement  of  this 
law  the  Public  Health  Service  has  promulgated  certain  regulations 
to  govern  those  engaged  in  the  manufacture  of  these  important  ther- 
apeutic products  and  has  established  standards  for  the  measurement 
of  the  potency  of  some  of  them. 

For  a  number  of  years  members  of  the  staff  of  the  Hygienic 
Laboratory  have  actively  cooperated  in  the  work  of  the  Council  on 
Pharmacy  and  Chemistry  of  the  American  Medical  Association,  the 
Committee  on  National  Formulary  of  the  American  Pharmaceutical 
Association  and  the  Committee  on  Non-official  Standards  of  that 
latter  Association. 

This  cooperative  work  done  by  members  of  the  staff  of  the 
division  of  pharmacology  in  connection  with  these  several  commit- 
tees is  no  doubt  familiar  to  you  and  need  not  be  specifically  reviewed 
at  this  time. 

The  division  of  pharmacology  of  the  Hygienic  Laboratory  has 
also  contributed  much  in  the  way  of  cooperative  work  on  the  revision 
of  the  pharmacopoeia  and  has  undertaken  the  study  of  a  number  of 
problems  in  connection  with  the  present  revision.  The  results  have 
from  time  to  time  been  published  either  in  the  form  of  bulletins  or 
in  papers  contributed  to  the  pharmaceutical  or  medical  journals. 
Up  to  date  these  studies  include:  The  standardization  of  thyroid 
products;  the  standardization  of  the  adrenal  gland  products,  more 
particularly;  the  standardization  of  epinephrine;  the  physiological 
standardization  of  the  official  preparations  of  digitalis  and  ^f  ergot; 
the  possible  standardization  of  tincture  of  caramel,  and  comprehen- 
sive investigations  on  the  solubility  and  on  the  melting  point  of 
official  chemical  substances. 

Of  even  more  direct  interest  to  pharmacists  as  an  illustration  of 
the  nature  of  cooperative  work  done  in  the  Hygienic  Laboratory  are 
the  publications  of  the  series  of  "  Digest  of  comments  on  the  Phar- 
macopoeia of  the  United  States  and  the  National  Formulary." 


AmApS"'i9i4.rm'}  United  States  Public  Health  Service.  161 

This  work  of  abstracting  the  literature  relating  to  the  Pharma- 
copoeia of  the  United  States  and  the  National  Formulary  was  under- 
taken at  the  request  of  the  board  of  trustees  of  the  United  States 
Pharmacopoeial  Convention,  with  the  sanction  of  the  Secretary  of 
the  Treasury,  and  the  compilations  have  appeared  in  the  form  of 
bulletins  covering  the  literature  of  the  calendar  years  from  1905  to 
date.  This  work  has  received  high  commendation  from  physicians, 
pharmacists  and  chemists  in  all  parts  of  the  world.  The  eminent 
pharmacognosist,  A.  Tschirch,  in  commenting  on  this  work,  admits 
that  practical  Americans  were  the  first  to  recognize  the  importance 
of  conserving  intellectual  energy  in  connection  with  the  revision  of 
the  pharmacopoeia  and  comments  favorably  on  the  comprehensive- 
ness of  the  "  Digest  of  Comments."  Pharmaceutical  and  medical 
journals  generally  have  commented  favorably  on  the  several  bulletins 
and  have  uniformly  voiced  the  opinion  that  these  bulletins  represent 
a  work  of  great  utility  and  because  of  the  fact  that  they  bring  to- 
gether with  remarkable  clearness  the  public  comments  on  pharma- 
cology and  materia  medica  and  thus  form  an  index  of  the  work  of 
the  year  such  as  is  not  published  elsewhere. 

In  addition  to  the  work  done  in  connection  with  the  pharma- 
copoeial revision  and  the  standardization  of  drugs  and  preparations, 
there  has  also  been  published  as  Public  Health  Bulletin  No.  56  a 
"  Digest  of  the  Laws  and  Regulations  in  Force  in  the  United  States 
Relating  to  the  Possession,  Use,  Sale,  and  Manufacture  of  Poisons 
and  Habit-Forming  Drugs."  This  is  the  first  complete  analytical 
compilation  of  the  laws  on  this  subject,  and  provisions  have  been 
made  to  keep  the  material  up  to  date  by  the  publication  of  new 
legislation  in  Public  Health  Reports  and  the  reprinting  of  this  mate- 
rial from  time  to  time  as  separates.  The  first  of  these  reprints, 
covering  the  legislation  enacted  during  1912  and  1913,  is  now  being 
distributed. 

As  an  illustration  of  the  relative  importance  of  matters  phar- 
maceutical to  public  health  work,  it  may  be  pointed  out  that  of  the 
90  bulletins  published  by  the  Hygienic  Laboratory,  no  less  than  39 
are  of  direct  interest  to  the  pharmacist,  or  have  some  distinct  bear- 
ing on  the  practice  of  pharmacy.  In  addition  to  the  7  volumes  on 
the  "  Digest  of  Comments,"  this  list  includes  the  very  popular  bul- 
letin of  122  pages  on  the  Changes  in  the  Pharmacopoeia  of  the 
United  States  of  America,  eighth  decennial  revision,  compiled  by 
Doctors  Reid  Hunt  and  Murray  Gait  Motter,  published  in  1905. 


1 62  United  States  Public  Health  Service.   \  Am  jour  pnarm. 

\      April,  1914.^ 

Six  bulletins  deal  specifically  with  the  physiological  standardization 
of  drugs,  four  deal  with  the  chemical  or  physical  standardization  of 
official  substances,  nine  discuss  the  use  and  standardization  of  anti- 
septics, disinfectants  and  germicides,  six  refer  more  specifically 
to  sera  and  vaccines,  and  six  involve  comprehensive  studies  of 
chemical  tests  and  other  problems  of  interest  to  pharmacy. 

In  addition  to  the  work  done  in  the  Hygienic  Laboratory  prac- 
tical observations  of  interest  to  pharmacists  are  from  time  to  time 
reported  by  individual  pharmacists  attached  to  the  several  stations 
in  different  parts  of  the  country. 

The  present  corps  of  pharmacists  includes  16  pharmacists  of 
the  first  class,  24  pharmacists  of  the  second  class,  and  6  pharmacists 
of  the  third  class. 

Sanitary  reports  and  statistics  and  the  results  of  scientific  inves- 
tigations are  of  value  only  as  they  are  made  public  and  used.  Among 
the  publications  issued  by  the  Service  are  the  Hygienic  Laboratory 
bulletins,  bulletins  of  the  Yellow  Fever  Institute,  Public  Health  bul- 
letins, the  weekly  public  health  reports,  and  miscellaneous  docu- 
ments. The  Hygienic  Laboratory  bulletins  represent  the  results  of 
scientific  investigations  conducted  in  the  laboratory.  The  public 
health  bulletins  are  popular  in  character,  and  are  utilized  to  convey 
sanitary  information  to  health  officials  and  to  the  public  generally. 
The  weekly  public  health  reports  are  issued  primarily  for  the  benefit 
of  health  authorities  as  an  aid  in  administration. 

Another  important  function  of  the  Public  Health  Service  in 
relation  to  the  public  health,  and  perhaps  the  most  important  one,  is 
the  conduct  of  scientific  investigations. 

By  an  act  of  March  3,  1901,  investigations  of  contagious  and 
infectious  diseases  and  matters  pertaining  to  the  public  health  were 
given  definite  status  in  law.  Provision  was  made  whereby  laboratory 
investigations  would  be  systematically  carried  on.  Through  this 
provision  and  in  connection  with  the  enforcement  of  the  quarantine 
laws  investigations  have  been  made  in  Washington  and  different 
parts  of  the  country.  In  order  to  comply  with  the  law,  however,  this 
work  was  carried  on  largely  through  the  Hygienic  Laboratory. 

By  an  act  of  Congress  approved  August  14,  1912,  broader  powers 
were  conferred  on  the  Public  Health  Service  to  "  study  and  inves- 
tigate the  diseases  of  man  and  conditions  influencing  the  propagation 
and  spread  thereof,  including  sanitation  and  sewage  and  the  pollu- 


Am.  Jour.  Pharm.  1 
April,  1914.  j 


Lecithin. 


tion,  either  directly  or  indirectly,  of  the  navigable  streams  and  lakes 
of  the  United  States." 

There  is  thus  abundant  authority  for  both  laboratory  and  field 
investigations  by  the  Public  Health  Service.  As  in  the  past  the 
investigations  will  be  conducted  by  officers  specially  trained  and  with 
such  cooperation  as  state  and  local  health  authorities  may  be  able 
to  render.  But  in  order  that  the  great  needs  of  the  country  may 
be  met,  more  men  and  more  money  must  be  provided  and  the  Public 
Health  Service  must  have  the  active  support  of  individuals,  profes- 
sional associations,  and  other  organizations  to  be  benefited. 

Many  highly  important  problems  await  solution.  Among  them 
may  be  mentioned  the  standardization  of  biologic  and  other  thera- 
peutic products,  the  determination  of  the  conditions  causing  pellagra 
and  certain  other  diseases,  the  extent  of  the  migrations  of  tubercu- 
lous and  other  patients  from  one  locality  to  another,  the  ascertain- 
ment of  the  influence  of  artificial  illuminants  on  health,  the  determi- 
nation of  the  relation  of  housing  and  other  conditions  to  labor 
efficiency,  and  the  prescribing  of  reasonable  standards  to  control 
stream  pollution. 

Requests  are  received  daily  from  all  parts  of  the  country  for  in- 
formation regarding  sanitary  problems  and  methods  of  handling 
them.  These  requests  are  an  excellent  indication  of  the  amount  and 
extent  of  work  to  be  performed  in  the  immediate  future.  In  one 
section  of  the  country  the  question  of  the  pollution  of  streams  is 
pressing  for  solution ;  in  another,  it  may  be  industrial  accidents  and 
poisoning;  in  another,  the  question  of  the  reduction  of  infant  mor- 
bidity; and  in  still  another,  the  measures  that  must  be  taken  to 
eradicate  malaria  and  other  communicable  disease. 


LECITHIN.* 

In  the  economy  oi  living  cells  belonging  to  the  vegetable  and 
animal  kingdoms,  a  very  important  part  is  played  by  a  certain  group 
of  bodies,  which  are  generally  spoken  of  collectively  as  "  lipoids."  1 

*  Reprinted  from  E.  Merck's  Annual  Report,  1912,  vol.  xxvi.,  pp.  1-22. 

1  The  word  "  lipoid  "  is  derived  from  the  Greek  "kt%oq  —  fat.  It  denotes 
fatty  substances  which  contain  phosphorus,  or  phosphorus  and  nitrogen,  or 
neither  of  these  elements,  and  which  have  special  functions  to  perform  in  the 
cell.    An  exact  definition  of  the  term  "  lipoid  "  cannot  be  given.  Kletzinsky 


164 


Lecithin. 


(  Am.  Jour.  Pharm. 
X      April,  1914. 


Among  the  best  known  members  of  this  group  are  the  cholesterins 
and  lecithins.  While  the  cholesterins  are  organic  combinations  free 
from  nitrogen  and  phosphorus,  the  lecithins  contain  both  nitrogen 
and  phosphorus.  They  are  grouped  together  as  a  special  class  of 
bodies,  the  so-called  "  phosphatides,"  2  comprising  a  large  number 
of  representatives.  The  phosphatides  are  characterized  by  contain- 
ing one  or  more  molecules  of  phosphoric  acid,  an  alcohol  (for  ex- 
ample glycerin),  one  or  more  fatty  acid  radicles  (for  example 
stearic  or  oleic  acid)  and  one  or  more  nitrogenous  bodies  (such  as 
choline  and  allied  substances).  Lecithin,  or  rather  the  lecithins,  are 
phosphatides  of  this  description.  The  theoretical  formula  of  the 
lecithins  is  as  follows: 


It  is  highly  probable  that  other  substances  containing  nitrogen  and 
allied  to  choline  may  occur  in  natural  lecithin,  but  so  far  choline  alone 
has  been  demonstrated  with  certainty  in  the  decomposition  products 
of  the  lecithins.  The  radicles  of  stearic,  palmitic  and  oleic  acid  (R  in 
the  above  formula)  are  present  in  the  form  of  esters  with  the  glyc- 
erin radicle  in  the  lecithin  molecule.  It  has  not  yet  been  possible 
to  determine  whether  one  molecule  always  contains  either  two  similar 
or  two  different  acid  radicles.    Although  in  the  examination  of 


understood  it  to  mean  those  substances  which  cannot  be  saponified  and  which 
may  be  extracted  from  animal  cells  by  means  of  alcohol  and  ether.  If  their 
non-saponification  be  left  out  of  account,  for  it  applies  to  cholesterin  but  not 
to  lecithin,  the  designation  "  lipoid  "  may  still  be  defined  in  the  terms  of  the 
author  mentioned  above,  for  Overton  considers  it  to  denote  all  those  com- 
ponents of  the  cell  which,  like  fat,  will  dissolve  in  ether,  chloroform  and 
similar  organic  liquids.  Kraus  termed  lipoids  "  noble  fats "  to  distinguish 
them  from  fats. 

2  Lecithin  is  a  mono-amino-mono-phosphatide,  which  denotes  that  still 
more  complex  substances  exist,  e.g.,  di-amino-mono-phosphatides,  mono- 
amino-di-phosphatides,  di-amino-di-phosphatides,  tri-amino-mono-phospha- 
tides,  etc.  These  bodies  have  not  as  yet  been  exhaustively  investigated.  (Com- 
pare Thudichum.) 

It  should  be  noted  that  at  the  end  of  the  original  article  in  Merck's 
Report  a  detailed  list  of  the  literature  is  given,  arranged  according  to  authors. 


/O.R 
C3H6^-0 .  R 


OH-$P=0 


/C2H4-0 
NHCH3)3 
\OH 


Am.  Jour.  Pharm.  \ 
April,  1914.  j 


Lecithin. 


165 


lecithin  obtained  from  egg  yolks  stearic  acid  and  palmitic  acid  or 
oleic  acid  are  usually  found,  this  is  not  a  proof  that  these  acids  are 
derived  from  a  single  molecule ;  for  a  mixture  of  stearyl  and 
palmityl-lecithin,  or  of  stearyl  and  oleic  acid-lecithin  may  equally 
well  be  present.  But  in  the  text-books  of  physiology  or  of  physio- 
logical chemistry,  lecithin  from  egg  yolks  is  occasionally  represented 
by  the  assumptive  formula  of  stearyl-palmityl-lecithin : 


The  structure  of  this  formula  may  most  probably  be  traced  back  to 
the  statements  of  Thudichum ;  in  his  opinion  a  lecithin  molecule 
always  contains  one  saturated  and  one  unsaturated  fatty  acid  resi- 
due. According  to  him,  every  true  lecithin  contains  at  least  one 
fatty  acid  radicle  and  always  represents  a  mono-amino-mono-phos- 
phatide, — e.g.,  the  molecule  contains  only  one  atom  of  nitrogen  and 
one  atom  of  phosphorus. 

It  is  generally  assumed  that  the  lecithin  from  egg  yolks  is  mainly 
stearyl-lecithin  and  the  lecithin  obtained  from  plants  mainly  oleic 
acid-lecithin.  In  how  far  this  assumption  is  supported  by  facts 
cannot  be  decided  on  the  strength  of  the  researches  on  the  lecithins 
so  far  carried  out.  It  is  indeed  doubtful  whether  the  above  formula 
definitely  explains  the  constitution  of  the  natural  lecithins.3  The 
investigations  of  MacLean,  Otolski,  Cousin,  Erlandsen,  Henriques 
and  Hansen  have  shown  that  the  lecithins,  besides  containing  cho- 
line, also  possibly  contain  other  nitrogenous  disintegration  products 
(pyridine)  and  other  unsaturated  fatty  acids  (linoleic  acid  and  lino- 
lenic  acid).  This  may  also  be  inferred  from  the  relatively  high 
iodine  number  of  the  lecithins,  which  is  not  sufficiently  explained 
by  their  content  of  oleic  acid.  Nor  can  it  be  decided  whether  cal- 
cium and  iron,  which  always  accompany  the  lecithins,  form  an 
essential  part  of  the  lecithin  molecule  or  are  merely  impurities ;  thus 
no  great  weight  can  be  attached  to  the  constitutional  formula  of 
lecithin.    Further,  Malengreau  and  Prigent,  as  a  result  of  hydro- 

8  According  to  Thierfelder  and  Stern,  other  phosphatides  besides  lecithin 
occur  in  egg  yolks.  These  have  also  been  found  by  Thudichum,  Hammarsten, 
Erlandsen  and  others  in  various  animal  organs. 


/  O .  CxsHwO 
C3H5— O .  CigHsiO 


OH— P=0 


/C2H4— O 
N=(CH3)3 


Lecithin. 


(Am.  Jour.  Pharm. 
\      April,  1914. 


lytic  experiments,  have  expressed  doubt  as  to  the  possibility  of  an 
ester-like  combination  between  choline  and  phosphoric  acid.  It  is 
certainly  true  that  the  natural  lecithins,  however  carefully  they  are 
purified,  always  represent  mixtures  of  various  lecithins.  The 
physical  condition  of  pure  commercial  lecithin,  which  is  waxy  and 
occasionally  somewhat  crystalline,  is  in  favour  of  this  view ;  and  it  is 
justifiable  to  assume,  according  to  the  present  position  of  research 
on  lecithin,  that  the  separate  lecithins  which  constitute  natural 
lecithin,  in  their  absolute  chemical  individuality  and  purity,  are 
crystalline  bodies. 

The  solution  of  this  problem  is,  however,  of  more  chemical  than 
physiological  or  therapeutic  interest.  As  is  evident  from  an  inves- 
tigation by  Stepp,  those  lecithins  alone  are  of  physiological  or  thera- 
peutic importance  which  are  produced  by  the  living  organism  itself 
for  its  own  use.  It  is  therefore  probably  justifiable  in  therapeutics 
to  speak  of  pure  lecithin  when  this  consists  solely  of  lecithins  with- 
out admixture  of  albumins  or  of  lecithalbumins.  My  Lecithinum*ex 
ovo  purissimum  is  a  preparation  of  this  nature. 

The  discovery  of  lecithin  is  usually  attributed  to  Gobley  (1846), 
although  long  before  him  Vauquelin  (1811)  and  Couerbe  (1834) 
found  and  described  phosphorus-containing  fats  in  the  brain,  which 
were  probably  identical  with  lecithin.  Fremy,  a  pupil  of  Couerbe, 
named  Vauquelin's  substance  "  oleo-phosphoric  acid,"  as  he  found 
its  products  of  decomposition  to  consist  of  glycerin,  phosphoric 
acid  and  oleic  acid.  In  conjunction  with  Valencienne  he  isolated  the 
same  substance  from  the  roe  of  fish.  But  Gobley  was  the  first  to 
prepare  it  from  the  yolk  of  eggs,  and  he  called  it  "  matiere  vis- 
queuse,"  and  later,  on  account  of  its  origin,  "  lecithin,"  from 
Aex-i&og  (=yolk  of  egg).4  He  was  also  the  first  to  recognise  the 
principal  component  of  lecithin  possessing  physiological  importance, 
namely  glycerophosphoric  acid,  which  is  obtained  by  the  careful 
saponification  of  lecithin;  he  thus  established  the  basis  for  the  con- 
stitution of  the  lecithin  molecule  which  is  still  fairly  generally 
accepted.  The  basic  component  of  lecithin,  choline,  was  discovered 
by  Liebreich  and  Strecker. 

Lecithin  is  therefore  regarded  as  a  glycerophosphoric  acid  in 


*  Strecker's  view  (Annalen  der  Chemie  und  Pharmazie,  1868,  Vol.  72,  p. 
77)  that  the  word  lecithin  is  derived  from  floe  (=  oil  jar)  and  should 
therefore  be  written  lecythin,  is  erroneous. 


Am.  Jour.  Pharm.  \ 
April,  1914.  J 


Lecithin. 


.OH 
C3H5^OH 

\CK  Glycerophosphoric  acid. 

OH^P=0 
OH/ 

which  the  hydrogen  atoms  of  the  hydroxyls  of  glycerin  are  replaced 
by  fatty  acid  radicles,  and  one  hydrogen  of  the  phosphoric  acid 
residue  by  a  choline  radicle.  Theoretical  consideration  shows  that 
two  possible  formulas  exist,  one  symmetrical  and  one  asymmetrical, 
according  to  the  position  of  the  fatty  acid  residues  in  the  glycerin, 
thus : 

/O .  R  /O  .  R 

C3H5^0 .  R  CHee-O- 


Vk  \0 .  R 

/C^-°o^0  oh:,p=o 

\OH 

Since  lecithin  is  optically  active  and  as,  according  to  Willstatter 
and  Liidecke  and  also  according  to  Power  and  Tutin,  the  glycero- 
phosphoric acid  derived  from  lecithin  possesses  rotatory  power, 
Ulpiani  expressed  himself  in  favour  of  the  asymmetrical  formula. 
Speculations  of  this  kind  are,  of  course,  only  of  theoretical  interest. 
Possibly  the  synthesis  of  the  lecithins,  which  has  not  as  yet  been 
successfully  carried  out,  will  throw  light  on  the  question  of  the 
constitution  of  lecithin.  Hundeshagen,  as  the  result  of  an  unsuc- 
cessful synthesis  of  lecithin,  claimed  to  have  proved  the  truth  of 
Strecker's  statement  that  lecithin  was  not  a  salt  of  di-stearyl-glycero- 
phosphoric  acid  and  choline,  but  an  ester-like  combination  of  the 
two  substances,  in  which  the  basic  character  of  choline  was  retained. 
The  choline  salt  of  di-stearyl-glycerophosphoric  acid  obtained  by 
Hundeshagen  had  quite  different  properties  than  lecithin.  Kade's 
attempts  to  prepare  lecithin  synthetically  must  also  be  regarded  as 
failures  from  a  practical  point  of  view. 

Occurrence  of  Lecithin. 

Lecithin  is  so  widely  distributed  in  the  human  and  animal  organ- 
isms that  it  has  been  concluded,  though  not  without  contradiction, 
that  no  organ  exists  which  does  not  contain  lecithin.  Thus  the 
phosphatide    is    found,    according    to    Hermann,  Hoppe-Seyler, 


Lecithin. 


(  Am.  Jour.  Pharm. 
\      April,  1914. 


Manasse,  Abderhalden  and  Peritz  in  the  blood;  according  to 
Miescher  in  pus ;  according  to  Gobley,  Liebreich,  Thudichum  and 
Koch  in  the  brain ;  according  to  Dunham,  Rubow,  Krehl,  Nerking, 
Heffter,  Baskoff,  Noel  Paton,  MacLean,  BischofT  and  others  in  the 
heart  (cardiac  muscle),  kidneys,  suprarenal  glands,  liver,  lungs  and 
spinal  cord,  and  according  to  Frankel  in  the  pancreas,  muscles,  tes- 
ticles and  submaxillary  gland  as  well;  according  to  Chevalier  and 
Koch  in  nerve  tissue  (sciatic)  ;  according  to  Glikin,  Rolle  and 
Otolski  in  bone  marrow ;  according  to  Thudichum,  Long  and  Gep- 
hart  in  bile;  according  to  Dezani,  Vacheron  and  Miescher  in  the 
sperm ;  according  to  Donath  in  the  cerebrospinal  fluid ;  according  to 
Wallis  and  Scholberg  in  ascitic  fluid,  etc.  Further,  according  to 
Hoppe-Seyler,  it  is  a  component  of  caviare;  according  to  Burow, 
Tolmatscheff,  Koch,  Vageler,  Siegfeld,  Glikin,  Dornic  and  Daire 
and  Marre  it  is  a  component  of  milk  and  consequently  of  butter,  as 
has  been  proved  by  Krampelmeyer,  Jaeckl  and  Bordas.  The  per- 
centage of  lecithin  indicated  by  the  various  authors  in  human  or 
animal  organs  is  as  follows : 


Blood  0.2  per  cent. 

Blood  corpuscles  0.46  per  cent. 

per  cent.) 
Brain  16  per  cent. 
Heart  4.5  per  cent. 
Cardiac  muscle  12.5  per  cent. 
Kidneys  8.5  per  cent. 
Suprarenal  gland  2.5  per  cent. 
Liver  4.3  per  cent 
Bile  0.15  per  cent. 
Lung  1.5  per  cent. 
Spinal  cord  11  per  cent. 
Marrow  3  per  cent. 
Pancreas  0.5  per  cent. 
Thymus  7.5  per  cent. 


Human  fat  0.05  per  cent. 
Muscles  0.8  per  cent. 
Testicles  1  per  cent. 
Submaxillary  gland  1  per  cent. 
Nerve  tissue  17  per  cent. 

(of  the  dry  tissue) 
Sciatic  nerve  33  per  cent. 

(of  the  dry  tissue) 
Sperm  1.5  per  cent. 
Milk  0.06  per  cent. 
Butter  0.17  per  cent. 
Yolk  of  egg  12  per  cent. 
Rabbit  (living)  0.5  per  cent. 
Hedgehog  (living)  0.8  per 

cent. 


1.8 


In  the  vegetable  kingdom  lecithin  is  also  very  frequently  found. 
It  was  first  discovered  in  plants  by  Knop  in  i860,  but  its  general  dis- 
tribution throughout  the  vegetable  kingdom  was  first  established 
by  Topler.  It  is  always  abundantly  present  in  seeds,  buds  and  young 
shoots,  a  fact  which  indicates  its  great  importance  in  the  growth  of 


Am.  Jour.  Pharm.  > 
April,  1914.  J 


Lecithin. 


169 


young  plants.  The  lecithin  content  of  various  seeds  is  specially 
reported  upon  by  Schulze,  Forti,  Maxwell,  Bernardini  and  Chia- 
rulli ;  lecithin  in  vegetable  oils  by  Schlagdenhauffen  and  Reeb,  Stell- 
waag,  Jacobson,  Riegel  and  others ;  in  sugar  cane  by  Shorey ;  in 
yeast  by  Hoppe-Seyler,  Himberg  and  Sedlmayr ;  in  leaves,  blossoms, 
fruits,  etc.,  by  Vageler  ;  in  fungi  by  Heinisch,  Zellner  and  Lietz;  in 
grape  pips  and  wine  by  Rosenstiehl,  Funaro  and  Barboni,  Muraro, 
Bicciardelli  and  Nardinocchi,  Salvadori  and  Mazzaron ;  and  the 
occurrence  of  lecithin  in  the  vegetable  kingdom  generally  by 
Kraetzschmar,  Heckel  and  Schlagdenhauffen,  Stoklasa,  Hanai, 
Marchlewski,  Winterstein  and  Fliestand  and  others. 

The  content  of  various  seeds,  vegetable  oils,  etc.,  is  given  as 
follows  in  the  literature : 


Barley  0.7  per  cent. 
Wheat  0.6  per  cent. 
Rye  0.6  per  cent. 
Peas  1.2  per  cent. 
Lentils  1  per  cent. 
Beans  0.8  per  cent. 
Linseed  0.9  per  cent. 
Vetch  seeds  1.2  per  cent. 
Lupin  seeds  2  per  cent. 
Pumpkin  seeds  0.4  per  cent. 
Poppy  seeds  0.25  per  cent. 
Maize  0.25  per  cent. 
Soya-bean  oil  0.15  per  cent. 
Ergot  1.7  per  cent. 
Toadstools  1.4  per  cent. 
Yellow  boletus  0.6  per  cent. 
Mushrooms  0.9  per  cent. 
Morel  1.6  per  cent. 


Cantharellus  cibarius  1.3  per  cent. 
Lettuce  0.36  per  cent. 
Rhubarb  0.33  per  cent. 
French  beans  0.25  per  cent. 
Green  peas  0.15  per  cent. 
Green  tomatoes  0.25  per  cent. 
Yeast  (dry)  2  per  cent. 
Wine  0.03  per  cent. 
Fat  of  melon  seeds  0.6  per  cent. 

"  "  lupin  seeds  7.5-50  per  cent. 
.  "     "  peas  30-50  per  cent. 

"     "  vetch  seeds  13-21  per  cent. 

"     "   rye  8  per  cent. 

"     "   wheat  7  per  cent. 

"     "  barley  7  per  cent. 

"     "  oats  11.5  per  cent. 

"     "   fenugreek  seeds  1.5  per  cent. 

"     "  maize  1.5  per  cent. 


However,  lecithin  does  not  only  occur  as  such,  but  especially  in 
plants  in  combination  with  other  substances.  Thus  ovo-vitellein,  de- 
scribed by  Hoppe-Seyler,  is  a  combination  of  lecithin  with  albumin ; 
jecorin,  described  by  Drechsel,  Boskoff,  Erlandsen  and  others,  is  a 
combination  of  lecithin  with  glucose  or  galactose  and  other  sub- 
stances ;  and  protagon,  which  occurs  in  the  central  nervous  system 
and  in  the  brain  and  has  been  investigated  and  described  by  Lieb- 
reich,  Hoppe-Seyler,  Diakonow,  Strecker,  Gamgee,  Blankenhorn, 


170 


Lecithin. 


f  Am.  Jour.  I'liann. 
|      April,  1U14. 


Baumstark,  Ruppel,  Kossel  and  Freytag,  is  a  combination  of  leci- 
thin with  cerebrosides.5  Protagon  is  described  by  Kossel,  Ruppel 
and  others  as  a  crystalline  substance,  soluble  in  hot  alcohol  and 
which  swells  up  in  water. 

Physiology  of  Lecithin. 

Special  attention  has  been  paid  to  the  study  of  the  origin  and 
significance  of  lecithin  in  the  vegetable  world  by  Maxwell,  Stoklasa, 
Staniski,  Marchlewski,  Hanai  and  Koch.  Even  though  the  results 
of  their  investigations  have  not  rendered  the  chemistry  of  lecithin 
formation  as  clear  as  might  be  desired,  yet  they  have  shown  that 
lecithin  may  and  usually  does  occur  in  all  parts  of  plants.  From 
this  fact  alone  it  may  be  concluded  that  it  is  a  very  important  or 
indispensable  body  in  the  plant. 

Maxwell  attempted  to  prove  that  the  phosphorus  present  in  seeds 
in  an  organic  form  was  changed  during  germination  to  the  organic 
form,  during  which  process  lecithin  was  produced.  The  interme- 
diate stages  passed  through  by  the  phosphoric  acid  are  unknown. 
In  the  transition  from  the  vegetable  to  the  animal  kingdom  the 
organic  combination  is,  in  the  author's  opinion,  retained.  The 
lecithin  of  a  hen's  egg,  on  the  other  hand,  changes  when  the  egg 
is  hatched  into  inorganic  phosphorus  compounds,  and  as  a  mineral 
phosphate  plays  a  part  in  the  bone-formation  of  the  developing 
animal.  But  in  the  later  stages  of  hatching,  as  Maxwell  showed, 
the  opposite  process  may  occur.  The  most  interesting  fact  brought 
out  by  Maxwell's  researches  is  that  the  animal  organism  is  capable 
of  changing  inorganic  phosphorus  into  organic  compounds.  As  in 
the  opinion  of  some  observers,  to  which  reference  will  be  made  later, 
the  lecithin  ingested  with  the  vegetable  food  is  decomposed  in  the 
animal  intestine  and  absorbed  as  phosphoric  acid  (glycerophosphoric 
acid),  lecithin  synthesis  must  occur  in  the  animal  and  human  organ- 
ism, for  it  would  otherwise  be  impossible  to  explain  the  origin  of  the 
richness  in  lecithin  of  the  animal  organism.  Reicher  has  recently 
also  favoured  this  opinion. 

Stoklasa,  from  his  own  observations,  formed  the  opinion  that 
by  far  the  greater  part  of  the  phosphoric  acid  of  plants  was  present 


6  Cerebrosides  are  bodies  containing  nitrogen  but  no  phosphorus,  which 
on  hydrolysis  produce  sugar. 


Am.  Jour.  Pharm.  ) 
April,  1914.  J 


Lecithin. 


171 


in  the  form  of  organic  compounds.  Besides  the  nuclein  compounds, 
lecithin  is  an  important  example  of  this  class.  It  probably  plays  an 
important  part  in  the  processes  of  assimilation  and  dissimilation. 
In  testing  the  lecithin  content  of  seedlings,  leaves  and  blossoms,  the 
author  found  that  the  lecithin  was  not  decomposed  by  germination, 
but  that  no  lecithin  was  formed  except  when,  under  the  influ- 
ence of  light  and  chlorophyll,  carbonic  acid  assimilation  had  set  in. 
He  even  showed  that  in  the  absence  of  chlorophyll  (in  the  leaves) 
no  lecithin  is  formed  and  that  in  etiolated  seedlings  the  lecithin  is 
used  up  or  decomposed.  It  is  possible  that  during  the  first  vegeta- 
tive period  lecithin,  under  the  influence  of  light,  assists  in  the  for- 
mation of  chlorophyll  in  the  seedling.  The  greatest  amount  of 
lecithin  is  probably  formed  in  fresh  green  leaves  at  the  time  when 
the  function  of  assimilation  is  at  its  height,  an  assumption  made 
probable  by  the  fact  that  the  amount  of  lecithin  in  leaf-buds  is  only 
half  as  great  as  that  in  fully  developed  leaves,  and  that  it  rapidly 
disappears  as  the  leaves  grow  older;  the  chlorophyll  is  reduced  and 
xanthophyll  makes  its  appearance.  According  to  this,  there  is  a 
close  connection  between  the  formation  of  chlorophyll  and  lecithin. 
Stoklasa  even  considers  that  lecithin  may  be  a  product  of  assimila- 
tion in  the  chlorophyll  corpuscle  itself.  In  agreement  with  this 
conjecture  is  the  observation  that  certain  plants,  if  placed  in  the 
dark  at  the  time  of  their  most  active  growth,  soon  show  a  consid- 
erable diminution  of  lecithin  in  their  leaves,  as  compared  with  those 
which  are  allowed  to  develop  in  the  light.  It  has  not  yet  been  dis- 
covered in  what  way  lecithin  assists  in  chlorophyll  formation,  but 
according  to  Stoklasa,  it  is  certain  that  no  chlorophyll  can  be  pro- 
duced in  the  absence  of  light  and  phosphorus.  Thus' even  if  lecithin 
is  not  a  part  of  the  chlorophyll  corpuscle  itself,  as  was  formerly 
assumed  by  Marchlewski,  yet  it  appears  to  participate  in  chlorophyll 
formation  and  to  supply  the  necessary  phosphorus.  From  the 
leaves  lecithin  travels  by  way  of  the  stems  into  the  blossoms,  where 
it  may  perhaps  assist  in  fertilisation,  and  thence  by  the  fruits  into 
the  seeds.  It  is  by  no  means  certain,  however,  that  the  green  leaves 
are  the  sole  producers  of  lecithin ;  it  is  quite  probable  that  plants 
and  animals  are  able  to  build  up  lecithin  in  certain  organs  and  from 
certain  substances,  as  is  the  case  for  example  in  yeast  and  in  fungi. 

Stoklasa' s  observation  that  phosphorus  is  present  in  plants  chiefly 
in  organic  form  is  confirmed  by  the  results  of  Staniski's  researches. 
This  observer  found  only  very  small  amounts  of  inorganic  phos- 


172 


Lecithin. 


{Am.  Jour.  Pharm- 
April,  1914. 


phoric  acid  in  the  seeds  of 'millet  in  comparison  with  the  amount  of 
organic  phosphorus  present.  He  found  that  in  millet  lecithin  for- 
mation was  at  its  height  during  the  period  of  seed  development,  and 
that  the  maximum  amount  of  lecithin  was  contained  in  the  plant 
during  the  period  of  panicle  formation.  Thus  it  is  justifiable  to 
draw  the  conclusion  that  lecithin  has  important  functions  to  perform 
in  connection  with  flower  and  seed  formation. 

Hoppe-Seyler  pointed  out  the  close  relationship  between  lecithin 
and  chlorophyll  mentioned  above.  He  even  placed  chlorophyll  in 
the  group  of  lecithins.  Although  this  view  has  not  as  yet  been  con- 
firmed, it  is  supported  to  some  extent  by  Stoklasa's  researches. 
Furthermore,  Marchlewski,  Bode  and  Kohl  have  put  forward  theo- 
retical considerations  according  to  which  chlorophyll  represents  a 
lecithin  in  which  the  fatty  acid  radicles  6  are  replaced  by  special, 
colored  complexes  (chlorophyllanic  acids),  or  these  complexes 
themselves  are  chlorophyll  combined  with  lecithin.7 

Hanai's  statements  supplement  Stoklasa's  communications.  He 
made  the  observation  that  the  old,  green  leaves  of  Thea  Chinensis 
lose  their  lecithin  in  spring,  and  that  the  young,  growing  leaves  are 
very  rich  in  lecithin.  He  therefore  places  lecithin  among  the  re- 
serve substances,  which  are  stored  in  certain  parts  of  the  plant  (as, 
for  example,  in  the  bark  of  the  plant  just  mentioned)  until  the  next 
period  of  growth,  when  they  are  supplied  to  the  new  shoots.8 

The  conclusions  drawn  by  Vageler  from  his  investigations  are 
deserving  of  special  mention.  According  to  these,  the  lecithins  are 
inseparably  bound  up  with  metabolism  and  with  the  vital  processes 
of  the  plant  generally.  The  content  of  phosphatides  increases  up  to 
the  time  of  development  of  the  fruit,  the  zenith  of  development,  and 
decreases  as  the  fruit  ripens.    Lecithin  has,  in  the  author's  opinion, 

11  Compare  the  formula  for  lecithin  on  page  164. 

7  According  to  W.  Pfeffer  (Pflanzenphysiologie,  1897,  2nd  edition,  Vol. 
1.  p.  478).  the  lecithins  are  perhaps  necessary  for  the  construction  of  proto- 
plasts. However,  it  is  not  yet  known  whether  they  take  part  in  the  con- 
version of  fats.  The  occurrence  of  choline  in  plants  probably  depends  upon 
the  conversion  of  lecithin.  According  to  Willstatter,  chlorophyll  contains 
no  phosphorus,  whereby  the  theories  of  the  authors  mentioned  above  are  in- 
correct. Compare  also  Marchlewski,  Biochemische  Zeitschrift,  1908,  Vol. 
10,  p.  131. 

8  According  to  Jost  (Pflanzenphysiologie,  1908,  p.  184),  however,  the  leci- 
thins are  not  reserve  substances,  but  constructive  materials  for  protoplasm, 
and  for  this  reason  they  are  not  decomposed  during  germination  of  the  seeds. 


Am.  Jour.  Pharm.  ) 
April,  1914.  j 


Lecithin. 


173 


probably  nothing  to  do  with  fat,  with  which  others  often  consider  it 
to  be  in  relation.  Like  Koch,  he  seeks  the  function  of  lecithin  in  the 
cell  primarily  as  an  oxygen  carrier,  but  also  in  the  colloidal  char- 
acter of  the  phosphatides,  "  for  the  substratum  of  life  itself,  proto- 
plasm, which  is  still  in  many  respects  so  enigmatical,  is  a  colloid." 

The  physiological  significance  of  the  fatty  acids  contained  in 
lecithin  and  of  choline  is  explained  by  Koch.  According  to  him, 
the  lecithins  are  of  importance  for  the  life  of  the  celi  in  two<  ways. 
For  in  conjunction  with  the  albumins  in  colloidal  solution,  they  con- 
stitute the  basis  for  the  formation  of  the  necessary  viscosity,  on 
account  of  the  ease  with  which  they  are  influenced  by  ions  (Na,  Caj. 
Further,  by  means  of  their  unsaturated  fatty  acids  they  take  part 
in  oxygen  metabolism,  and  by  their  methyl  groups,  which  are  com- 
bined with  nitrogen,  in  other  reactions  not  yet  known.  Phosphoric 
acid,  although  in  some  respects  the  nucleus  of  the  whole,  does  not, 
in  Koch's  opinion,  play  any  part  in  metabolism ;  Halliburton  has 
shown  that  the  amount  of  phosphorus  in  degenerated  nerves  does 
not  begin  to  decrease  before  the  eighth  day.  The  author  explains 
the  fact  that  the  residues  of  the  unsaturated  fatty  acids  are  capable 
of  taking  part  in  oxygen  metabolism  by  the  ease  with  which  they 
are  oxidised ;  this  is  also  known  to  be  the  case  with  lecithin  which 
has  been  in  contact  with  the  air  for  some  time.  But  it  has  not  yet 
been  proved  that  the  lecithins  may  be  regarded  as  oxygen  carriers. 
The  physiological  significance  of  the  nitrogen  group  may,  according 
to  Halliburton,  be  recognised  by  the  fact  that  in  certain  diseases  of 
the  nervous  system,  such  as  general  paralysis,  a  considerable  amount 
of  choline  passes  into  the  cerebrospinal  fluid. 

As  in  the  vegetable  kingdom,  so  in  the  animal  kingdom,  lecithin, 
as  I  mentioned  above,  is  present  in  almost  every  organ.  It  is  present 
in  comparatively  large  amounts  in  the  principal  organs,  and  the 
conclusion  may  consequently  be  drawn  that  it  also  performs  impor- 
tant functions  in  the  economy  of  the  animal  cell.  The  nature  of 
these  functions  cannot  be  stated  with  certainty.  Nor  has  it  been  con- 
clusively ascertained  whether  lecithin  is  formed  in  the  animal  or- 
ganism, whether  it  is  ingested  with  the  food,  or  whether  both  these 
processes  take  place.  The  results  of  the  investigations  of  various 
observers  afford  some  elucidation  of  the  matter. 

Bokay  found  that  lecithin  was  split  up  in  the  intestine  by  the 
fat-splitting  ferment  of  the  pancreas,  or  putrefactive  ferment,  into 
fatty  acids,  choline  and  glycerophosphoric  acid.    As  he  was  unable 


Lecithin. 


J  Am.  Jour,  tharm. 
\       April,  1914. 


to  demonstrate  the  presence  of  phosphoric  acid  in  ethereal  and 
alcoholic  extracts  of  the  faeces,  he  concluded  that  lecithin  or  its 
decomposition  products  were  absorbed  and  used  up  by  the  organism. 
In  agreement  with  this  conclusion  is  the  fact  investigated  by  him 
that  the  amount  of  phosphoric  acid  in  the  urine  is  substantially  in- 
creased after  the  ingestion  of  lecithin.  Glycerophosphoric  acid  is 
absorbed  from  the  intestine  in  the  form  of  a  salt,  and  is  not,  accord- 
ing to  Hasebrok,  further  broken  down  into  glycerin  and  phos- 
phoric acid.  Grosser  and  Husler,  on  the  other  hand,  think  it  im- 
probable that  glycerophosphoric  acid  passes  directly  from  the  intes- 
tine into  the  organism,  as  they  succeeded  in  isolating  a  ferment,  the 
so-called  glycerophosphotase,  from  the  intestinal  and  renal  cells 
which  splits  up  glycerophosphoric  acid  without  leaving  a  residue. 
They  therefore  assume  that  lecithin  is  completely  broken  down  in 
the  intestine  and  is  built  up  again  from  its  elements  in  the  tissues. 
The  fatty  acids,  like  the  fats  taken  in  with  the  food,  are  partially 
absorbed  in  the  form  of  salts  of  fatty  acids  and  partially  excreted. 
Choline  is  further  broken  down  with  formation  of  carbonic 
acid,  ammonia  and  methane.  As  lecithin  is  said  to  be  com- 
paratively readily  broken  down,  it  is  probably  safe  to  assume  that 
lecithin  is  not  absorbed  as  such  in  the  intestine ;  but  this  does  not 
prove  that  it  may  not  be  partially  absorbed  unaltered  and  carried 
to  the  circulation.  Miescher's  observation  on  Rhine  salmon  is  gen- 
erally cited  as  a  typical  example  of  lecithin  formation  in  the  animal 
organism.  According  to  this,  a  comparatively  large  amount  of 
lecithin  is  formed  in  the  sexual  organs  of  these  fishes  during  the 
hunger  period,  which  is  said  to  occur  as  they  wander  up  stream. 
The  necessary  phosphorus  is  presumably  supplied  by  certain  muscles 
of  the  fish.  Paton  also  attempted  to  prove  that  in  salmon  inorganic 
phosphorus  changes  into  organic  phosphorus  ;  however,  the  asser- 
tions of  Paton  and  Miescher  can  only  be  accepted  if  it  be  proved 
that  during  their  sojourn  in  fresh  water  these  fishes  really  take  in 
no  nourishment.  This  was  doubted  by  Putter.  Rohmann,  from 
experiments  on  mice,  concludes  that  the  animal  organism  is  capable 
of  forming  lecithin,  for  the  mice  increased  and  continued  their  de- 
velopment on  lecithin-free  food.  But  in  similar  experiments  car- 
ried out  by  Stepp  and  Rohl  the  experimental  animals  perished. 
According  to  Rohl,  mice  fed  exclusively  on  rice  always  perish 
in  a  few  weeks,  whereas  on  the  addition  of  a  small  amount  of 
lecithin  their  development  continues  normally.    He  therefore  con- 


Am.  Jour,  riiarm.  1 
April,  1914.  J 


Lecithin. 


175 


siders  lecithin  to  be  an  essential  component  of  food,  which  cannot 
be  constructed  from  its  elements  in  the  mammalian  body.  On  the 
other  hand,  according  to  Fingerling's  observations,  ducks  are  appar- 
ently able  to  produce  large  amounts  of  lecithin  from  inorganic  phos- 
phorus. It  must  also'  be  assumed  that  glycerophosphoric  acid  which 
has  been  absorbed  is  made  use  of  in  certain  organs  for  the  produc- 
tion of  lecithin.  The  choline  required  for  this  purpose  has  been 
shown  to  be  present  in  various  parts  of  the  organism  (Kinoshita  °) . 
Mulon,  Bernard  and  others  point  to  the  suprarenal  glands  as  the 
seat  of  formation  of  lecithin.  Moreover,  lecithin  appears  to  be 
capable  of  being  split  up  by  ferments  in  certain  organs.  Coriat, 
for  example,  believes  an  enzyme  to  be  present  in  the  brain,  which 
decomposes  lecithin  with  separation  of  choline.  He  did  not  succeed 
in  isolating  this  enzyme,  but  he  proved  that  its  action  was  destroyed 
by  heating. 

After  Bokay  had  demonstrated  that  lecithin  could  be  split  up 
by  the  secretion  from  the  small  intestine,  P.  Mayer  attempted  to 
establish  which  of  the  ferments  of  the  small  intestine  (trypsin,  erep- 
sin,  lipase)  caused  this  disintegration.  He  found  that  lecithin  was 
abundantly  split  up  by  steapsin  and  that  under  certain  conditions 
the  fatty  acids  separated  in  a  crystalline  form.  According  to  this, 
the  behaviour  of  lecithin  is  identical  with  that  found  by  Connstein  in 
the  fermentative  decomposition  of  the  true  fats.  Mayer  believes 
his  observations  to  show  that  the  enzymes  do  not  react  in  the  same 
way  upon  d-  and  1-lecithin. 

SchumofT-Simanowski  and  Sieber  also  confirm  the  action  of 
pancreatic  and  g*astric  'steapsin  in  splitting-  up  lecithin,  whereas 
their  tests,  with  lipase  of  blood  or  blood  serum  gave  a  negative  re- 
sult. It  is  not  capable  of  splitting  off  fatty  acids  from  lecithin.  It 
is  indeed  possible,  with  the  help  of  this  negative  character,  to  dis- 
tinguish lipase  from  other  lipolytic  enzymes.  Lecithin  is,  on  the 
other  hand,  decomposed  by  vegetable  ferments,  especially  by  the 
ferment  of  Ricinus  communis,  with  separation  of  fatty  acids. 

But  the  results  of  the  authors  mentioned  above  do  not  appear  to 
correspond  entirely  with  all  the  facts,  if  they  are  compared  with 

0  Choline  is  said  by  Lohmann  to  occur  in  the  suprarenal  glands,  by  von 
Fiirth  and  Schwarz  in  the  thyroid  gland  and  intestinal  extracts,  by  Schwarz 
and  Lederer  in  the  thymus,  spleen  and  lymphatic  glands,  by  Kutscher  in  flesh, 
by  Letsche  in  serum,  by  Jacobsen  in  bile,  by  Cramer  in  the  brain,  by  Bohm 
in  the  placenta,  by  Gautrelet  in  the  kidneys,  ovaries,  testicles  and  pancreas. 


176 


Lecithin. 


Am.  Jour.  Pharni. 
April,  1914. 


the  results  obtained  by  Slowtzoff,  Stassano  and  Billon.  According 
to  these  authors,  lecithin  is  not  by  any  means  readily  decomposed  and 
it  is  doubtful  whether  it  is  decomposed  by  the  action  of  putrefactive 
bacteria  and  pancreatic  ferment.  Thus  Stassano  and  Billon  found 
that  neither  activated  pancreatic  juice  nor  gastric  juice  acts  upon 
lecithin;  this  was  confirmed  by  SlowtzofT  for  fresh  lecithin,  but  he 
observed  the  decomposition  of  older  (oxidised)  lecithin.  He  also 
confirmed  the  observation  that  choline  was  separated  from  lecithin 
which  had  been  stored  for  some  time,  even  when  boiled,  alkaline 
ferment  solution  was  used.  Independently  of  the  separation  of  cho- 
line, saponification  of  lecithin  by  means  of  pancreatic  juice, — e.g., 
by  steapsin,  apparently  occurs.  As  lecithin  is  readly  emulsified  in 
the  presence  of  bile  and  albumoses,  and  as  Stassano  and  Billon 
claimed  to>  have  observed  that  lecithin,  when  injected  subcutaneously, 
was  taken  up  by  the  leucocytes  which  had  migrated  to  the  site  of 
injection,  and  that  by  feeding  on  lecithin  the  latter  apparently  passed 
into  the  lymph  of  the  thoracic  duct,  SlowtzofT  conducted  experiments 
which  showed  that  lecithin,  when  administered  internally,  is  in  part 
ingested  unchanged,  as  could  be  recognised  by  the  appearance  of 
lecithin  in  the  lymph.  As  regards  the  splitting  up  of  lecithin  in  the 
intestine,  it  occurs,  according  to  SlowtzofT,  in  the  duodenum  where 
it  cannot,  in  his  opinion,  be  caused  by  putrefactive  bacteria. 

The  results  of  the  investigations  of  the  observers  mentioned 
above  lead  to  the  assumption  that  the  lecithin  taken  in  witji  the 
food  is  partly  absorbed  as  such  and  partly  split  up.  SlowtzofT  as- 
sumes that  like  the  fats  it  can  be  gradually  reconstructed  in  the 
organism  by  synthesis.  The  proof  of  this  may  be  sought  in  the  fact 
that  the  same  or  very  similar  results  have  been  achieved  in  therapy 
with  the  salts  of  glycerophosphoric  acid  (compare  Merck's  Report 
191 1,  pages  1  to  30)  as  with  lecithin. 

With  regard  to  the  action  on  lecithin  and  its  decomposition  by 
ferments  (lipase,  diastase)  reference  may  also  be  made  to  the  pub- 
lications of  Lapidus  and  Terroine. 

The  investigations  carried  out  by  Glikin  are  of  much  value  for 
the  biological  significance  of  lecithin.  He  points  out  that  birds  and 
mammals  show  a  greater  or  less  content  of  lecithin  in  the  bones  or 
the  whole  body,  according  as  to  whether  they  are  born  naked  and 
helpless,  or  independent  and  with  their  senses  developed.  Thus  the 
amount  of  lecithin  in  cats  and  dogs,  which  are  born  blind  and  help- 
less, is  greater  than  that  in  guinea-pigs,  which  immediately  after 


A  in.  Jour.  Phariii.  ( 
April,  l'J14.  / 


Lecithin. 


177 


birth  are  able  to  feed  on  cabbage  and  turnips  like  the  fully  devel- 
oped animals  and  are  not  dependent  upon  mother's  milk;  similarly 
insessorial  birds  contain  more  lecithin  than  autophagous  birds,  which 
is  indeed  clearly  shown  in  the  eggs  of  these  birds.  Man,  also, 
who  comes  into  the  world  helpless,  shows  a  very  high  percentage  of 
lecithin  in  the  bone  marrow,  which  is  only  appreciably  diminished 
when  growth  proceeds  more  slowly,  or  ceases.  He  also  established 
the  fact  that  the  bone  marrow  of  young  animals  contains  far  more 
lecithin  than  does  that  of  fully  developed  animals,  and  that  this 
store  of  lecithin  diminishes  as  the  animal  grows  and  that  new- 
born animals  come  into-  the  world  with  a  large  supply  of  lecithin. 
From  these  observations  it  is  evident  that  lecithin  represents  a 
highly  significant  factor  in  the  growth  of  animals,  even  though 
nothing  is  yet  known  of  the  finer  biological  processes  involved  in  the 
utilisation  of  lecithin  in  the  cell  and  in  the  organism. 

But  in  order  to  form  a  conception  of  the  functions  of  the  lecithins 
or  of  the  lipoids  in  general,  the  colloidal  nature  of  these  substances 
must  primarily  be  taken  into  account;  and  also  their  capability 
of  forming  solutions  and  compounds,  which  are  readily  decomposed, 
with  other  substances  of  importance  in  the  construction  and  the  life 
of  the  cell.  It  must  also  be  taken  into'  consideration  that  certain 
concentrations  of  lipoids  are  more  soluble  in  solutions  of  alkaline 
salts  than  in  other  salt  solutions.  It  is  assumed  that  by  an  increase 
in  the  concentration  of  the  salt  by  the  entrance  of  calcium  salts  into 
the  cell  with  consequent  separation  in  flakes  of  the  lipoids,  mem- 
branes are  formed  which  are  permeable,  impermeable  or  semi-per- 
meable to  certain  solutions.  The  so-called  semi-permeable  mem- 
branes, especially,  appear  to  be  of  importance  to  the  life  of  the  cell, 
as  they  serve  to  keep  within  bounds  the  entrance  and  exit  of  sub- 
stances. 

In  the  interior  of  the  cell,  according  to  Meyer,  it  is  through  the 
intervention  of  the  lipoids  that  the  whole  of  the  contents  do  not  join 
to  form  a  homogeneous  mass,  but  that  the  thousand  particles  form- 
ing the  cell,  with  all  their  different  chemical  affinities,  remain  side 
by  side,  drawn  up  in  order  and  at  a  measured  distance ;  on  the  sur-  - 
face,  however,  they  constitute  a  guard  against  too  rapid  streaming 
in  and  out  of  water,  and  against  the  penetration  of  all  the  salts 
dissolved  in  the  blood  and  in  the  tissue  fluids,  and  of  other  sub- 
stances. They  also  form  a  sort  of  sieve  for  the  penetration  of  sub- 
stances soluble  in  fat,  especially  of  those  which  dissolve  more  readily 


i7S 


Lecithin. 


Am.  Jour  J'lianii. 
April,  1914. 


in  lipoids  than  in  water  and  aqueous  albumin-colloids.  The  action 
of  narcotic  drugs  stands  in  close  relation  with  this  solubility  in 
lipoids.  It  may  also  be  assumed  that  the  functions  of  the  lipoids 
may,  within  certain  limits,  be  modified  by  their  different  chemical 
construction, and  solubility  in  the  body  juices,  as  well  as  by  reciprocal 
solution.  For  it  is  known  that  the  solubility  of  the  best  known 
lipoids,  lecithin  an.d  cholesterin,  may  be  altered  in  other  fluids  by 
mixing  the  two  substances.  Erlandsen  found  that  lecithin,  which 
by  itself  is  insoluble  in  acetone,  became  soluble  to  a  slight  degree  in 
the  presence  of  cholesterin.  It  must  further  be  taken  into  considera- 
tion that  the  lecithin  of  the  organism  includes  a  large  number  of 
similarly  constructed  substances,  which  occur  in  mixtures  in  various 
proportions,  and  on  account  of  the  varying  concentrations  of  salt 
solutions  are  differently  influenced  and  precipitated  or  redissolved. 

The  permeability  for  albumins  and  inorganic  (calcium,  alkali 
and  phosphoric  acid )  salts  of  the  semi-permeable  membranes  formed 
by  the  lipoids,  which  is  confirmed  by  the  fact  that  the  organic  lipoids 
contain  inorganic  salts  of  this  kind,  facilitates  the  perception  of  the 
electrical  processes  which,  in  the  opinion  of  various  observers,  take 
place  in  the  cell.  Thus  Hober  and  Nernst  have  developed  theories 
which  are  intended  to  explain  the  connection  between  galvanic  proc- 
esses in  the  organ  tissues  and  the  stimulation  of  nerve  activity. 

The  physiological  processes  which  take  place  in  the  cells  between 
lecithin  and  narcotic  drugs  are  of  great  pharmacological  interest. 
Harlen  and  von  Bibra  considered  the  narcotic  action  of  ether  and 
chloroform  to  be  due  to  the  liberation  of  fat  by  these  drugs  in  the 
cells  of  the  brain.  Hermann  assumed  that  the  narcotic  drugs  ^at- 
tacked the  lecithins  and  cholesterins  of  the  ganglion  cells.  H. 
Meyer  came  nearer  to  the  truth  when  he  ascertained  that  the  action 
of  a  narcotic  drug-  was  the  more  powerful  the  more  readily  it  dis- 
solved in  lipoids  and  the  less  readily  it  was  soluble  in  water.  This 
was  also  confirmed  by  Overton.  In  his  opinion  the  narcotic  drugs 
pass  into  those  components  of  the  cell  which  contain  cholesterin 
and  lecithin,  and  alter  their  physical  condition  in  such  a  way  as  to 
disturb  their  functions,  or  to  act  injuriously  upon  the  functions  of 
other  components  of  the  cells.  This  alteration  of  function  very 
probably  depends  upon  a  sort  of  anchoring  of  the  narcotic  to  the 
lipoids,  the  bond  being  weakened  by  the  introduction  of  other  lipoids. 
This  at  least  follows  from  Nerking's  experiments.  This  observer 
administered  to  animals  simultaneously  intravenous  injections  of 


And.  Jour.  l*harru.  | 
April,  1914.  / 


Lecithin. 


1 79 


lecithin  and  urethane  and  found  that  the  usual  prompt  action  of 
urethane  remained  absent.  He  concluded  that  urethane,  injected 
simultaneously  with  the  lecithin,  became  anchored  to  the  latter  and 
was  thus  unable  to  enter  into  reciprocal  action  with  the  lipoids  of 
the  brain.  Further  experiments  with  ether,  chloroform,  morphine, 
scopolamine,  novocaine,  tropacocaine  and  stovaine  gave  a  similar 
result.  The  subcutaneous,  intravenous  and  intraperitoneal  injec- 
tion of  these  narcotics,  applied  simultaneously  with  lecithin,  always 
caused  an  earlier  return  to  consciousness,  or  the  earlier  reappear- 
ance of  sensation.  Similarly,  animals  which  had  previously  received 
an  injection  of  lecithin  required  a  larger  dose  of  the  narcotic  than 
those  which  had  not  previously  undergone  lecithin  treatment.  These 
results  justify  the  conclusion  that  lecithin  injections  might  be  em- 
ployed for  human  beings  also,  in  order  to  shorten  the  period  of 
narcosis  or  as  a  prophylactic  against  its  troublesome  secondary 
effects.  For  experiments  of  this  nature  subcutaneous  injections  of 
aqueous  emulsions  of  lecithin  or  intravenous  injections  of  lecithin- 
sodium  chloride  emulsions  are  suitable. 

The  part  played  by  lecithin  in  haemolysis  by  poisons  is  also  of 
physiological  significance.  In  1902  Flexner  and  Noguchi  made  the 
observation  that  blood  corpuscles,  which  had  been  completely  freed 
from  the  adherent  serum  by  washing  with  physiological  salt  solu- 
tion, were  not  dissolved  by  snake  venom.  They  assumed  that  a 
substance  was  present  in  the  blood  serum  which  played  the  part  of 
activator  of  the  amboceptors  of  the  snake  venom,  and  this  was  later 
experimentally  demonstrated  by  Kyes.  According  to  Kyes,  cobra 
venom  which  is  inactive  towards  various  kinds  of  blood  immediately 
assumes  hemolytic  properties  on  the  addition  of  lecithin.  If  cobra 
venom  occasionally  causes  solution  of  blood  corpuscles  in  spite  of 
the  absence  of  serum,  it  is  due,  according  to<  Kyes  and  Sachs,  to  the 
lecithin  contained  in  the  blood  corpuscles ;  and  this  occurs  more 
readily  the  more  loosely  the  lecithin  is  bound  to  the  blood  corpuscle 
or  to  the  molecule  of  protoplasm.  The  communications  of  Abder- 
halden  and  le  Count  show  that  the  activating  properties  of  lecithin 
may  be  arrested  by  cholesterin. 

Finally,  the  relationship  existing  between  the  action  of  lecithin 
and  that  of  Rontgen  rays  or  radium  rays  has  gained  the  considera- 
tion of  physiologists.  Reference  may  be  made  to  the  communica- 
tions on  this  subject  by  Schwarz,  Werner,  Exner,  Sywek,  Neuberg, 
Wohlgemuth  and  Hoffmann. 


i8o 


Lecithin. 


(  Am.  jour.  Pharm. 
[      April,  1914. 


The  Importance  of  Lecithin  in  Metabolism  and  Nutrition. 

After  the  favourable  effect  of  lecithin  upon  phosphorus  metab- 
olism and  upon  nitrogen  metabolism  had  been  established,  first  by 
Selenski  and  later  by  Serono  and  Charrin,  Desgrez  and  Zaky,  ex- 
perimenting on  animals,  proved  that  feeding  with  lecithin  leads  to 
a  lasting  retention  of  phosphorus.  According  to  their  observations, 
phosphorus  is  used  for  bone-formation  and  for  building  up  the 
brain;  they  were  also  able  to  prove  that  after  feeding  with  lecithin 
the  amount  of  lecithin  in  the  brain  was  appreciably  increased.  The 
favourable  influence  exerted  by  lecithin  upon  metabolism  in  general 
and  upon  retention  of  phosphorus  in  particular,  led  the  two  observers 
to  undertake  more  exhaustive  observations  on  guinea-pigs,  in  which 
they  found  that  it  was  not  the  glycerophosphoric  acid,  but  the  choline 
which  diminished  the  excretion  of  phosphorus  and  causes  an  in- 
crease in  the  body-weight, — e.g.,  that  the  action  of  lecithin  depends 
upon  its  basic  components.  Hatai  was  able  to  confirm  the  favourable 
influence  exerted  by  lecithin  upon  growth.  He  treated  white  rats 
belonging  to  one  and  the  same  brood,  some  with  lecithin  and  some 
without,  and  obtained  the  surprising  result  that  the  animals  treated 
with  lecithin  thrived  considerably  better,  indeed  they  increased  in 
body-weight  by  60  per  cent,  more  than  the  other  animals.  Internal 
administration  brought  about  the  best  results,  but  better  growth 
of  the  animals  was  also  observed  after  subcutaneous  administration. 

Danilewski  noticed  that  tadpoles  grew  with  extraordinary 
rapidity  under  the  influence  of  lecithin,  and  he  therefore  tried  the 
drug  in  young  dogs.  He  found  that  the  subcutaneous  and  internal 
administration  of  lecithin  is  a  great  incentive  to  bodily  growth,  im- 
provement of  the  blood  and  increase  of  the  brain,  which  he  explains 
as  an  acceleration  of  the  bioplastic,  morphogenous  processes.  He 
observed  especially  that  the  dogs  treated  with  lecithin  appeared 
much  more  lively,  more  intelligent  and  physically  stronger  than 
the  control  animals.  For  his  experiments  he  employed  an  emulsion 
of  lecithin  in  physiological  salt  solution,  of  which  he  injected  doses 
of  0.02  to  0.05  gramme  of  lecithin  under  the  skin  of  the  abdomen, 
or  gave  double  this  dose  by  mouth.  In  further  experiments  on  the 
blood-forming  properties  of  the  spleen  and  the  bone  marrow, 
Danilewski  and  Selenski  arrived  at  the  conclusion  that  lecithin  plays 
an  important  part  in  the  haematopoietic  processes  which  take  place 
in  these  organs.    This  assumption  gains  in  probability  when  it  is 


Am.  Jour.  Pharm.  ) 
April,  1914.  | 


Lecithin. 


181 


borne  in  mind  that  lecithin  is  capable  of  adsorbing  and  binding  in 
the  organism  various  substances  of  importance  in  the  vital  process, 
•such  as  albumins,  sugars,  salts,  ferments,  etc.,  substances  which  for 
their  part  are  readily  decomposed  into-  their  components. 

An  insight  into  the  relations  which  exist  in  metabolism  under  the 
cooperation  of  lecithin  is  also  furnished  by  the  results  of  the  inves- 
tigations of  Franchini,  Massaciu,  Buchmann,  Zuntz,  Yoshimoto  and 
Slowtzoff.  According  to  Franchini,  feeding  rabbits  on  lecithin  in- 
creases the  lecithin  content  especially  in  the  liver,  less  in  the  muscles 
and  not  at  all  in  the  brain.  The  increase  in  the  lecithin  content  of 
the  liver  remains  for  some  time,  even  after  the  ingestion  of  lecithin 
has  been  discontinued.  The  discovery  of  the  author  that  only  very 
little  lecithin  is  excreted  in  the  faeces  tallies  with  other  statements 
which  have  been  mentioned  above.  Franchini  also'  confirmed  the 
observation  that  during  lecithin  administration  an  increased  amount 
of  glycerophosphoric  acid  is  found  in  the  muscles  and  in  the  liver. 
He  also'  found  a  slight  increase  of  this  acid  in  the  urine,  though  this 
may  have  been  first  formed  from  lecithin  in  the  urine,  for  lecithin 
is  a  somewhat  labile  substance.  The  fact  that  no  choline  could  be 
found  in  the  urine  is,  however,  not  in  favour  of  this  view. 

The  choline  which  is  split  off  from  the  lecithin  during  metab- 
olism is,  according  to  the  author,  further  broken  down  and  oxi- 
dised in  the  organism,  and  appears  as  formic  acid  in  the  urine. 
Another  hypothesis  which  has  not  yet  been  proved  has  been  sug- 
gested by  Low.  He  assumes  that  lecithin  acts  in  metabolism  as  a 
fat-carrier,  the  fatty  acids  being  split  off  from  the  molecule  and  then 
replaced  by  new  ones.  Part  of  the  lecithin-phosphorus  is,  accord- 
ing to  Yoshimoto  and  Buchmann,  kept  back  for  some  time  in  the 
organism  and  is  most  probably  only  very  gradually  excreted.  Be- 
sides retention  of  phosphorus,  Yoshimoto,  Zuntz  and  Slowtzoff  also 
found  retention  of  nitrogen,  which  was  not  always  accompanied  by 
an  increase  in  body-weight.  Voltz  and  Massaciu  also  observed  an 
increase  in  the  albumin  content  after  feeding  dogs  and  guinea-pigs 
on  lecithin,  whereas  Rogozinski  was  unable  to  demonstrate  either 
an  increase  in  nitrogen  or  phosphorus. 

These  experiments  on  animals,  the  results  of  which  are  in  part 
contradictory,  have  long  been  rendered  perfectly  clear  by  means  of 
the  practical  employment  of  lecithin  in  man.  The  investigations  on 
metabolism  carried  out  by  Cronheim  and  Miiller  on  several  children 
(under  a  year  old)  are  interesting.    On  feeding  with  children's 


Lecithin. 


Am.  Jour.  Pharm. 
April,  1914. 


meal  (consisting  of  skim  milk  powder,  oatmeal  and  sugar)  and 
administering  lecithin,  the  nitrogen  of  the  food  was  better  assimi- 
lated and  retained  by  the  body  than  was  the  case  when  lecithin  wa$ 
not  administered  simultaneously.  In  the  former  case  the  nitrogen  re- 
tention amounted  to  19  to  28  per  cent.,  in  the  latter  case  only  to  2  to 
24  per  cent.  On  the  other  hand,  as  regards  phosphorus  retention,  food 
containing  lecithin  showed  no  advantages,  nor  could  any  influence 
on  fat  and  carbohydrate  metabolism  be  observed.  Calcium  and  mag- 
nesium salts  were,  however,  held  back  by  the  lecithin,  which  is  a 
point  in  favour  of  increased  bone-formation.  The  older  the  chil- 
dren, the  more  evident  was  the  favourable  influence  of  lecithin.  This 
phenomenon  is  perhaps  due  to  the  fact  that  the  body  of  the  suckling 
contains,  according  to  SiwertzerT,  a  large  store  of  lecithin,  which  is 
gradually  used  up  in  the  course  of  the  first  4  to  5  months  of  life. 
Thus,  children  under  5  months  of  age  are  so  richly  supplied  with 
lecithin  that  a  further  supply  becomes  superfluous  and  cannot  be 
utilised.  The  utility  of  the  drug  really  first  becomes  apparent  when 
the  store  of  lecithin  has  been  exhausted. 

Recent  experiments  by  Cronheim  show  that  lecithin  is  not  only 
valuable  during  growth,  but  is  also  of  value  to  adults.  A  fully 
developed  individual  requires  a  certain  amount  of  lecithin  for  the 
maintenance  of  normal  metabolism.  It  is  therefore  justifiable  to 
assume  that  the  drug  is  as  beneficial  for  adults  as  for  children. 

Massaciu  carried  out  the  following  metabolism  experiment  on  a 
man  :  he  was  first  given  meat  and  no  lecithin,  in  the  second  experi- 
mental period  he  received  roborat  containing  lecithin,  and  in  the 
third  period  he  was  given  both  meat  and  lecithin.  The  assimila- 
tion of  nitrogen  was  increased  threefold  in  the  second  period  as 
compared  with  the  first,  the  nitrogen  being  better  utilised  in  the 
intestine.  The  same  occurred  in  the  third  period.  This  furnished 
a  further  proof  of  the  nitrogen-sparing  power  of  lecithin.  The 
author  also  observed  retention  of  phosphorus  during  lecithin  admin- 
istration. Marfori's  results  are  in  agreement  with  this;  he  found 
that  egg-lecithin,  when  subcutaneously  applied,  furnished  the  or- 
ganism with  phosphorus  capable  of  being  assimilated. 

Moricheau  Beauchamp  experimented  on  himself  and  on  a  med- 
ical student  and  found  a  nitrogen-sparing  and  phosphorus-sparing 
action.  The  author  administered  0.5  to  1  gramme  of  lecithin  a  day 
and  found  after  4  days  that  he  had  gained  in  energy  and  that  his 
weight  had  increased  by  900  grammes.  In  the  urine  he  found  a 
decrease  of  nitrogen,  urea,  phosphoric  acid  and  xanthin  bodies. 


TAKr-}  Lecithin.  183 

The  value  of  lecithin  in  nutrition  is  also  shown  in  a  paper  by 
Usuki.  The  author  found  in.  experiments  on  dogs  that  lecithin  has 
a  favourable  influence  on  the  saponification  of  neutral  fat,  and  that 
it  thus  accelerates  the  digestion  of  fat.  As  regards  digestion  in 
general,  the  only  doubtful  point  is  whether  lecithin  exerts  a  favour- 
able or  a  harmful  influence  upon  it,  or  upon  the  digestive  ferments. 
This  point  has  not  yet  been  settled.  Certain  conclusions  may,  how- 
ever, be  drawn  from  the  communications  of  Hewlett,  Furth,  Schiitz, 
Kiittner,  KalaboukofT  and  Terroine.  Furth  and  Schiitz  found  that 
bile  has  the  power  of  augmenting  the  action  of  the  fat-splitting 
and  albumin-splitting  pancreatic  ferments,  which  they  consider  to 
be  closely  connected  with  the  presence  of  bile  salts.  Nencki  had 
previously  made  a  similar  observation.  Hewlett,  on  the  other  hand, 
considered  the  favourable  influence  upon  these  ferments  to  be  due 
to  the  lecithin  content  of  bile ;  Furth  and  Schiitz  were  only  able  to 
confirm  this  in  the  case  of  an  alcoholic  solution  of  lecithin.  Kiittner 
attempted  to  test  more  carefully  the  influence  of  lecithin  upon  the 
digestive  ferments  ;  he  came  to  the  conclusion  that  definite  additions 
of  lecithin  sometimes  hasten  and  sometimes  delay  the  enzyme  action 
of  gastric  or  pancreatic  juice.  He  was,  however,  unable  to  offer  a 
reliable  explanation  of  the  matter.  KalaboukofT  and  Terroine 
have  expressed  the  decided  opinion  that  diastatic  ferments  are 
not  influenced  by  lecithin.  The  results  of  their  investigations  are 
as  follows:  "The  addition  of  lecithin  to  pancreatic  juice  never 
hastens  its  decomposing  action  on  monobutyrin ;  it  hastens  very 
slightly  the  action  upon  oil,  but  only  in  relatively  high  concentra- 
tions. The  lipolytic  action  of  glycerin  extracts  of  gastric  mucous 
membrane  remains  unaltered  by  the  addition  of  lecithin ;  intestinal 
lipase  is  unaltered  by  the  addition  of  lecithin.  The  addition  of 
lecithin  has  no  effect  upon  the  rapidity  of  starch  hydrolysis,  of  diges- 
tion of  casein  and  coagulated  albumin,  or  upon  the  coagulation  of 
milk  and  pancreatic  juice."  These  results  throw  doubt  upon  Hew- 
lett's view  mentioned  above.  The  communications  of  Bang,  Wohl- 
gemuth, Lapidus  and  Starkenstein  also  show  that  lecithin  does  not 
possess  the  accelerating  action  assigned  to  it  by  Hewlett. 

Slowtzoff,  as  a  result  of  his  lecithin  experiments  on  man,  came 
to  the  conclusion  that  lecithin  occasioned  retention  of  nitrogen,  ac- 
companied by  a  diminution  of  sulphuric  acid  excretion  in  the  urine. 
He  considers  this  to  be  related  to  the  decomposition  of  albuminous 
bodies,  and  concludes  that  what  occurs  is  retention  of  albumin  and 
not  retention  of  other  nitrogenous  products  (extractives).    In  his 


184 


Book  Reviews. 


f  Am.  Jour.  Pharm. 
t      April,  1914. 


opinion,  the  assimilation  of  albumin  runs  parallel  with  the  assimila- 
tion of  phosphoric  acid  and  the  diminution  of  the  albuminous  sub- 
stances. This  phenomenon  shows  that  lecithin  promotes  the  organi- 
sation of  albumin, — e.g.,  its  transformation  into  tissue-albumin. 
This  transition  of  absorbed  into  organised  albumin  must,  accord- 
ing to  Umikoff  and  SlowtzofT,  be  considered  as  being  due  to  the 
addition  to  the  albumin  of  phosphoric  acid  and  xanthin  bodies. 
Thus,  according  to  SlowtzofT,  lecithin  acts  favourably  upon  this  or- 
ganisation, and  it  is  comprehensible  for  the  increased  assimilation 
of  albumin  to  be  accompanied  by  the  retention  of  xanthin  bodies 
and  of  phosphoric  acid. 


BOOK  REVIEWS. 

Allen's  Commercial  Organic  Analysis.  Vol.  III.  Enzymes, 
Proteins  and  Albuminoid  Substances,  Milk  and  Milk  Products,  Meat 
and  Meat  Products,  Haemoglobin  and  Blood,  Proteids  and  Fibroids. 
Edited  by  W.  A.  Davis  and  Samuel  S.  Sadtler  and  the  following 
contributors :  E.  F.  Armstrong,  S.  B.  Schryver,  L.  L.  van  Slyke, 
Henry  LefTmann,  Cecil  Revis,  W.  D.  Richardson,  J.  A.  Gardner, 
E.  R.  Bolton,  G.  A.  Buckmaster,  W.  P.  Dreaper  and  Jerome  Alex- 
ander. Philadelphia:  P.  Blakiston's  Son  &  Co.,  1012  Walnut  Street. 
1913.    $5.00  net. 

This  is  another  volume  of  Allen's  Commercial  Organic  Analysis 
which  contains  very  much  matter  of  special  interest  to  pharma- 
cists. Indeed,  every  article  contains  information  that  is  likely  to  be 
wanted  either  for  purposes  of  manufacture  or  in  analytical  work. 
The  article  on  haemoglobin  and  its  derivatives,  by  John  A.  Gardner 
and  George  A.  Buckmaster,  is  one  of  the  most  succinct  articles  on 
the  practical  examination  of  blood  that  we  have  seen.  A  similar 
commendation  may  be  made  of  the  articles  on  "  Proteins  of  Milk,"  by 
L.  L.  van  Slyke,  "  Milk,"  by  Dr.  Henry  LefTmann,  "  Milk  Prod- 
ucts," by  C.  Revis  and  E.  R.  Bolton,  and  "  Meat  and  Meat  Products," 
by  W.  D.  Richardson. 

In  addition  to  the  article  on  the  "  Proteins  of  Milk  "  there  are 
two  other  chapters  on  these  highly  complex  nitrogenous  substances. 
The  one  on  "  The  Proteins  and  Albuminoid  Substances  "  by  S.  B. 
Schryver  and  the  other  on  "  Proteins  of  Plants  "  by  J.  Frankland 
Armstrong.    While  the  monograph  on  plant  proteins  may  not  con- 


Am.  Jour.  Ptiarrn.  > 
April,  1914.  j 


Current  Literature. 


185 


tain  as  much  general  information  as  the  work  of  T.  B.  Osborne  on 
"  The  Vegetable  Proteins, "  yet  it  contains,  probably,  the  essentials 
for  all  analytical  work. 

Among  the  other  valuable  articles  are  those  on  "  Enzymes  "  by 
E.  Frankland  Armstrong  and  on  "  Albuminoids  in  Scleroproteins  " 
by  Jerome  Alexander.  In  some  respects,  this  chapter  on  the  albu- 
minoids by  Mr.  Alexander  is  one  of  the  most  interesting  in  the  whole 
volume.  The  word  albuminoid  is  restricted  by  the  biological  chem- 
ists of  America  to  simple  proteins  which  exhibit  pronounced  insolu- 
bility in  all  neutral  solvents.  On  the  other  hand,  as  many  of  these 
protein  substances  form  the  chief  constituents  of  the  skeleton  of 
animals  as  well  as  of  the  skin  and  its  appendages,  the  physiological 
chemists  of  England  apply  the  term  scleroproteins  to  them.  Alex- 
ander classifies  these  substances  as  follows:  (1)  Collagens  or  jelly- 
forming  albuminoids;  (2)  Fibroids;  (3)  Chitinoids ;  and  (4) 
Keratins. 

CURRENT  LITERATURE. 
Formalized  Gelatin  Capsules. 

Enteric  Capsules  (Hard  and  Soft  Gelatin). — Used  for  medi- 
cines which  are  apt  to  produce  gastric  disturbance,  such  as  Potas- 
sium Iodide,  Oil  of  Santalwood,  Sodium  Salicylate,  Sodium  Car- 
bonate, Creosote,  Sodium  and  Zinc  Phenolsulphonate,  etc. 

Ballenger  and  Elder  suggest  the  immersion  of  the  filled  capsule 
for  one  minute  in  a  dilution  of  1  part  of  40  percent.  Formaldehyde 
Solution  in  from  40  to  60  parts  of  water.  The  capsules  should  be 
allowed  to  stand  for  two  weeks  after  immersion  before  use. 

Another  method  is  to  subject  the  filled  capsules  to  the  vapor  of 
Solution  of  Formaldehyde  as  follows : 

Place  the  capsules  in  an  open  box  in  a  vessel  which  can  be  tightly 
closed.  Take  15  Cc.  of  40  percent.  Formaldehyde  Solution  for  each 
cubic  foot  of  space  in  the  vessel  and  pour  it  on  cotton  or  gauze 
spread  out  upon  a  dish  in  the  vessel. 

Six  hours'  exposure  to  the  vapor  is  sufficient  for  capsules  which 
are  not  to  be  used  immediately.  Twelve  hours'  exposure  is  prefer- 
able for  capsules  required  for  immediate  use.  These  estimates  are 
for  soft  elastic  capsules  kept  at  room  temperatures  (from  70  0  to 
75°  F.). 


Current  Literature. 


{Am.  Jour.  Pharm. 
April,  1914. 


Another  plan  suggested  to  secure  intestinal  absorption  is  to  in- 
corporate the  medicament  in  a  mixture  of  suet  and  paraffin.  The 
stomach  contains  no  fat  digestant  and  the  mass  will  pass  into  the 
intestines.    The  following  combination  is  suggested  : 

Sodii  Carbonatis  Monohydratis  or 
Potassii  Iodidi  or 

Sodii  Salicylates    90  Gm. 

Sevi    30  Gm. 

Paraffini    16  Gm. 

M.  ft.  mass. 

Melt  all  ingredients  together  on  a  water-bath  and  encapsulate 
in  No.  00  gelatin  capsules. 

To  test  the  efficiency  of  the  method  prepare  test  capsules  of 
methylene  blue  and  oil  of  santol. 

Two  hours  after  administration  the  eructation  following  the 
taking  of  a  carbonated  water  will  indicate  whether  or  not  the  capsule 
has  broken  in  the  stomach.  If  the  capsules  have  been  hardened  too 
greatly  by  the  formaldehyde,  the  fact  will  be  indicated  by  very  slow 
coloring  of  the  urine  by  the  methylene  blue. 

Mr.  Smith,  in  his  Thesis,  advises  the  placing  of  the  filled  cap- 
sules in  a  ten  percent,  solution  of  formaldehyde  during  fifteen 
minutes,  then  washing  them  in  running  water  for  twenty  minutes. 
The  capsules  are  afterward  dried  in  a  dish  in  a  water-bath  for  five 
hours  or  until  free  from  the  odor  of  formaldehyde.  They  have  been 
used,  in  his  experience,  for  the  administration  of  Sodium  Phenosul- 
phonate  and  Zinc  Phenolsulphonate.  (See  Thesis  of  N.  L.  Smith, 
P.  C.  P.,  1912,  vol.  5  ;  also  Ballenger  and  Elder,  in  lour.  A.  M.  A., 
1914,  p.  197.) 

E.  F.  Cook. 
Deterioration  of  Nitroglycerin  Tablets. 

Rippetoe  &  Smith  (Journal  A.  Ph.  A.,  January,  19 14,  96)  report 
the  results  of  several  experiments  which  lead  them  to  conclude  that, 
"  nitroglycerin  will  volatilize  in  the  process  of  making  the  tablets  if 
the  granulation  is  exposed  for  any  length  of  time,  but  after  com- 
pressing the  tablets  and  storing  in  ordinary  corked  bottles  very 
little  deterioration  takes  place. 

"  The  tablets  will  lose  in  strength  if  exposed  in  unstoppered 
bottles,  therefore  containers  that  are  not  air  tight,  such  as  cardboard 
boxes,  should  not  be  used." 


Am.  Jour.  Pharm.  * 
.April,  1914.  I 


Current  Literature. 


187 


The  assays  were  made  by  the  modified  Scoville  method,  which 
they  consider  to  be  a  very  practical  and  reliable  method. 

"Samples  of  0.01  (1/100)  and  0.02  (1/50)  grain  hypodermic 
tablets,  which  were  assayed  on  April  12,  191 2,  having  been  made 
some  time  previous,  were  set  aside  on  a  laboratory  shelf  in  ordinary 
cork  stoppered  glass  tubes  of  100  each.  These  tablets  were  assayed 
by  the  modified  Scoville  method  on  November  12,  19 13,  with  the 
results  as  shown  in  the  following  table : 

April  12,  1912.  November  12,  1913- 

0.02  grain  0.0150  grain  0.0149  grain 

0.01  grain  0.0061  grain  0.0057  grain 

''These  tablets  while  they  were  deficient  in  nitroglycerin  when 
made  show  practically  no  loss  during  a  period  of  19  months. 

"  A  10  per  cent,  solution  of  nitroglycerin  (strength  was  not  con- 
firmed by  analysis)  was  mixed  with  sugar  of  milk  to  give  a  nitro- 
glycerin content  of  5  per  cent.  This  mixture  upon  analysis  was 
found  to  contain  4.13  per  cent,  of  nitroglycerin.  A  quantity  of 
hypodermic  tablets  was  made  up  from  this  mixture  using  the  theo- 
retical amount  based  upon  the  above  analysis  to  give  a  tablet  assay- 
ing 0.01  grain.  The  tablets  upon  assaying  were  found  to  contain 
0.0102  grain  nitroglycerin.  These  tablets  were  handmade  while 
a  lot  of  tablet  triturates,  which  were  made  from  a  granulation  on  p. 
machine  using  the  same  quantities  as  above,  assayed  0.0093  grain 
nitroglycerin. 

"  Two  bottles  each  containing  about  100  of  0.02  grain  tablet 
triturates,  made  in  1907,  were  set  aside  in  a  closet,  one  of  the  bot- 
tles being  corked  and  the  other  having  only  a  piece  of  muslin  over 
the  mouth  of  the  bottle  to  exclude  dust.  These  tablets  were  assayed 
in  November,  1913,  by  the  modified  Scoville  method  after  having 
been  stored  as  stated  above  for  six  years  with  the  following  results : 

Tablets  in  stoppered  bottle   0.0130  grain 

Tablets  in  unstoppered  bottle    0.0040  grain 

"  In  all  probability  these  tablets  would  not  have  assayed,  by  the 
modified  Scoville  method,  much  over  0.015  grain  when  made.  (Com- 
pare assay  tablets  in  first  experiment  April  12,  19 12.) 

What  Is  Soap? 

Certain  resolutions  passed  at  a  recent  meeting  of  the  Ohio  State 
Pharmaceutical  Association  regarding  the  description  of  soap  cer- 


Current  Literature. 


(  Am.  Jour.  Pharm. 
\      April,  1914. 


tainly  need  to  be  accepted  with  a  considerable  amount  of  reservation. 
Copies  of  the  resolutions  passed  at  the  meeting  were  furnished  to  the 
State  Authorities  of  the  Federal  Department  of  Agriculture  and  the 
Revision  Committee  of  the  United  States  Pharmacopoeia  and 
National  Formulary. 

The  following  were  the  actual  resolutions  adopted : 

"  Whereas,  The  market  is  flooded  with  various  mongrel  soaps, 
masquerading  as  Castile  Soap ;  and 

"  Whereas,  The  Designation  Castile  Soap  has  long  been  recog- 
nized as  and  held  to  refer  to  U.  S.  P.  Soap ;  therefore  be  it 

"  Resolved,  That  we  recommend  the  adoption  of  such  State  and 
National  Standards  as  will  forbid  the  use  of  the  term  '  Castile  '  as 
applied  to  any  soap  other  than  the  U.  S.  P.  Soap ;  and  be  it  further 

"  Resolved,  That  we  recommend  the  incorporation  of  the  term 
Castile  Soap  as  a  synonym  for  Sapo  in  the  forthcoming  Pharma- 
copoeia ;  and  be  it  further 

"  Resolved,  That  copies  of  these  resolutions  be  furnished  to  & 
State  Authorities,  the  Federal  Department  of  Agriculture,  and  th: 
Revision  Committee  of  the  U.  S.  P.  and  N.  F." 

Now  we  question  very  much  whether  the  description  "  Castile 
Soap  "  is  one  that  should  be  maintained  at  all,  and  in  connection  at 
any  rate  with  British  pharmacy  it  should  not  be  forgotten  that  the 
name  "  Castile  Soap  "  as  a  synonym  for  hard  soap  was  abandoned 
in  the  British  Pharmacopoeia  of  1898,  although  it  was  official  in  the 
Pharmacopoeia  of  1885. 

The  hard  soaps  of  various  Pharmacopoeias  are  described  in  a 
variety  of  ways,  and  in  one  case  only  does  the  title  indicate  that  the 
source  should  be  Spanish,  namely,  the  Russian  Pharmacopoeia,  which 
describes  hard  soap  as  Sapo  Hispanicus  Albus. 

The  following  are  the  titles  employed  in  the  various  Pharma- 
copoeias, and  we  see  no  reason  why  the  British  Pharmacopoeia  title 
should  not  be  one  generally  adopted : 

In  the  United  States  Pharmacopoeia  simply  Sapo ;  Belgian 
Pharmacopoeia,  Sapo  Officinalis  ;  Danish  and  Dutch,  Sapo  Medicatus  ; 
Hungarian,  Sapo  Venetus ;  Norwegian,  Sapo  Albus  Oleaceus ; 
Spanish,  Jabon  de  Sosa ;  Swedish,  Sapo  Medicatus ;  Swiss,  Sapo 
Oleaceus. 

It  is  a  pity  that  in  certain  works  of  reference,  notwithstanding 
that  the  synonym  Castile  Soap  has  been  officially  dropped,  the  soap 
should  be  so  described  or  referred  to.   For  example,  in  Squire's  Com- 


Am.  Jour.  Pharm.  > 
April,  1914.  / 


Current  Literature. 


panion  to  the  British  Pharmacopoeia,  edition  1908,  under  the  solu- 
bility test,  reference  is  made  to  the  digestion  of  30  grs.  of  white 
Castile  Soap  in  1  oz.  of  cold  alcohol  90  per  cent.,  when  only  24  grs. 
were  dissolved,  whilst  in  the  recently  published  Codex,  under  Hard 
Soap,  the  description  is  "  Hard  or  Castile  Soap,"  thus  assuming  that 
Castile  Soap  is  a  synonym  for  hard  soap.  It  is  well  recognized  in 
commerce  that  the  soap  now  supplied  as  Castile  Soap  is  prepared 
from  a  variety  of  other  oils  than  olive  oil. 

The  resolutions,  therefore,  that  have  been  adopted  by  the  Ohio 
Pharmaceutical  Association  must,  in  the  light  of  commerce  of  to- 
day, be  vieweci  with  some  considerable  amount  of  reserve.  Editorial 
in  "Perfumery  and  Essential  Oil  Record/'  September,  191 3. 

Pharmaceutical  Education. — Dr.  H.  Thorns  writes  in  a  very 
informative  and  comprehensive  manner  on  the  question  of  prelim- 
inary educational  requirements  and  pharmaceutical  training  in  Ger- 
many and  other  European  countries.  It  is  worthy  of  note  that  he 
lays  particular  stress  on  the  value  to  a  student  of  a  good  prelimi- 
nary education.  If  he  possesses  that  valuable  asset,  an  asset  that  is 
the  foundation  of  success  in  any  calling,  he  will,  other  things  being 
equal,  be  able  to  overcome  what  would  otherwise  seem  insurmount- 
able obstacles  with  ease  and  facility.  It  is  proverbial  that  in  building 
operations  the  stability  of  the  superstructure  depends  upon  a  well- 
laid  foundation.  So  with  pharmacy  or  any  of  the  learned  pro- 
fessions. 

It  is  also  worthy  of  observation  that  the  general  trend  of  exami- 
nations in  determining  a  candidate's  fitness  to  practise  his  calling 
is  toward  practical  laboratory  work.  Written  and  oral  examina- 
tions, combined  with  practical  laboratory  work,  are  the  order  of  the 
day  in  Germany  as  well  as  in  most  other  European  lands.  This 
desirable  condition  has  obtained  in  Germany  for  many  years,  as 
has  likewise  the  necessity  of  students  possessing  a  good  general 
education  for  entrance  to  the  study  of  a  profession. 

It  does  not  require  a  great  intellect  to  see  and  appreciate  the 
value  of  further  educational  development  along  these  lines.  It 
means  so  much  to  the  general  welfare  of  a  community  from  the 
stand-point  of  safeguarding  the  public  health.  Men  of  Thoms's 
type,  both  here  and  abroad,  are  emphasizing  this  more  and  more 
every  day. 

Not  only  is  the  pharmacist  expected,  nay,  legally  required,  to 
stand  between  the  physician  and  the  patient,  but  he  must  be  able, 


190  Current  Literature.  {AmApdir'i9i4arm" 

in  these  days  when  he  (the  pharmacist)  depends  to  such  a  large 
extent  upon  the  manufacturing  pharmacist  for  his  pills,  tablets,  solu- 
tions in  ampules,  tinctures,  and  extracts  both  solid  and  fluid,  and  other 
pharmaceuticals,  to  stand  as  a  bulwark  of  protection  between  the 
manufacturer  and  the  consumer.  In  other  words,  the  pharmacist 
is  responsible  for  the  purity  and  accuracy  of  dosage  of  all  medicines 
dispensed,  whether  made  by  himself  or  a  manufacturing  house. 

And  in  order  to  accept  and  shoulder  this  responsibility  he  must 
be  thoroughly  grounded  in  the  principles  of  the  allied  branches 
which  comprise  the  science  and  art  of  pharmacy.  He  must  be 
familiar  with  and  capable  of  using  modern  methods  and  apparatus 
for  the  investigation  of  chemicals  and  galenical  preparations ;  he 
must  be  able  to  make  analyses,  both  of  inorganic  and  organic  chem- 
icals; he  also  should  be  able  to  make  microscopical  examinations 
of  sections  of  vegetable  drugs  and  powdered  drugs;  in  short,  he 
should  be  a  pharmacognist ;  he  should  be  thoroughly  conversant 
with  the  underlying  principles  governing  bacteriology,  as  the  use  of 
sterile  solutions  and  preparations  by  physicians  is  becoming  more 
prevalent  every  day  and  it  is  logical  that  the  pharmacist  should  be 
looked  to  as  a  source  to  supply  this  demand. 

Thorns  makes  it  perfectly  clear.that  this  development  of  pharmacy 
along  lines  of  greater  scientific  efficiency  is  not  by  any  means  Uto- 
pian ;  that  there  is  great  need  of  better  efficiency  among  the  rank 
and  file  of  the  profession,  and  that  it  is  quite  possible  and  practicable 
for  the  student  of  today  to  receive  the  necessary  training  for  the 
realization  of  this  object.  If  pharmacy  is  to  continue  to  exist  on 
a  scientific  basis  its  proper  development  must  be  along  a  rigorous 
scientific  curriculum. — Arbeiten  aus  dem  Pharmaseutischen,  Institut 
der  Universitat,  Berlin,  vol.  x,  page  189,  191 2. 

John  K.  Thum. 

Radium  and  Radium  Salts.1 

Radium  is  a  bivalent  metallic  element  closely  related  to  barium. 
It  is  exceedingly  reactive,  making  it  difficult  to  isolate  in  its  metallic 
state  and  after  isolation  to  keep  in  a  pure  state,  as  it  reacts  with  air, 
forming  the  oxide,  nitrite  and  finally  the  carbonate.  On  account  of 
this  activity  it  is  only  produced  in  the  form  of  its  salts,  principally 
as  the  bromide,  chloride,  sulphate  and  carbonate. 


1  Jour.  Amer.  Med.  Assoc.,  January  3,  1914,  p.  41. 


Am.  Jour.  Pliarm.  ) 
April,  1914.  } 


Current  Literature. 


191 


The  most  important  property  of  radium  is  its  radio-activity  upon 
which  depends  its  therapeutic  value.  Radio-activity  is  defined  as 
"  the  property  of  spontaneously  emitting  radiations  capable  of  pass- 
ing through  plates  of  metal  and  other  substances  opaque  to  ordinary 
light  and  having  the  power  of  discharging  electrified  bodies."  A 
spontaneous  disintegration  of  the  atoms  characterizes  all  the  radio- 
active elements  and  it  is  in  this  transmutation  or  splitting  of  the 
atom  that  the  rays  are  shot  out,  some  being  material  in  nature,  others 
electrical  or  of  the  nature  of  light.  This  spontaneous  transmutation 
of  radium  is  going  on  at  a  regular  rate,  which  is  independent  of  the 
state  of  combination  of  radium  in  the  molecule  of  its  compounds. 

To  determine  the  radio-active  value  of  radium,  use  is  made  of  its 
property  of  ionizing  gases.  Thus  when  radium  is  allowed  to  act  on 
the  air  in  a  charged  gold-leaf  electroscope  the  air  becomes  ionized 
and  therefore  a  conductor  of  electricity  and  allows  the  charge  to 
leak  out,  causing  the  leaf  in  the  electroscope  to  move.  By  observing 
the  rate  of  movement  of  the  leaf  in  a  calibrated  apparatus  the  radio- 
activity can  be  determined. 

Quantities  and  concentrations  of  radium  emanation  are  expressed 
in  terms  of  "  curies  "  and  Mache  units.  A  "  curie  "  is  the  amount 
of  emanation  in  equilibrium  with  1  gram  of  radium;  a  microcurie, 
one  millionth  of  a  "  curie,"  is  the  amount  of  emanation  in  equilibrium 
with  0.001  mg.  radium  and  is  equivalent  to  about  2,500  Mache  units. 

Relation  of  Radium,  -Radium  Emanation  and  Rays. — The  rays 
are  largely  derived  indirectly  from  radium  through  the  formation 
of  its  "  active  deposit,"  according  to  the  following  scheme : 

aparticle 

/ 

Rad.  aparticle 

\  / 

eman. 

\ 

ac.  dep. sh^t: Rays. 

These  rays  are  divided  into  three  groups,  the  alpha,  beta  and 
gamma,  which  differ  in  their  velocity  and  penetrative  power.  The 
alpha  and  beta  rays  consist  of  minute  particles  of  matter  electrically 
charged  and  moving  with  a  velocity  almost  equal  to  that  of  light. 
They  are  for  the  most  part  of  relatively  feeble  penetrating  power. 
The  gamma  rays  are  vibrations  in  the  ether,  very  similar  to  X-rays, 
and  of  high  penetrating  power.  Therapeutically  the  last  group  is 
the  most  useful. 

Radium  emanation  is  continuously  given  off  from  aqueous  solu- 


192 


Current  Literature. 


(Am,  Jour.  Pharm. 
\       April,  1914. 


tions  of  radium  salts.  It  can  be  collected  as  it  escapes  from  the 
solution,  drawn  off  through  the  use  of  the  mercury  pump,  or  by 
other  suitable  means,  quantitatively  determined  by  either  the  alpha 
or  gamma  ray  electroscope,  brought  into  solution  in  water  for  in- 
ternal or  external  use  or  be  set  free  in  an  emanatorium  for  inhalation 
treatment.  It  may  be  collected  into  small  glass  containers  and  this 
used  in  place  of  the  applicators  described  under  surgical  use. 

Actions  and  Uses:  Radium  emanation  is  said  to  increase  the 
excretion  of  uric  acid  in  the  urine  and  to  decrease  its  concentration 
in  the  blood ;  to  increase  somewhat  the  number  of  red  blood-cor- 
puscles ;  to  cause  temporary  leukocytosis  early  in  the  course  of 
treatment,  the  mononuclear  increase  being  relatively  greater ;  to  lead 
frequently  through  long-continued  use  to  leukopenia,  although  no 
appreciable  benefit  is  observed  in  leukemia.  It  is  said  that  radium 
increases  general  metabolism,  and  in  vitro  activates  certain  enzymes, 
pepsin,  pancreatin,  rennin,  autolytic  ferments,  tyrosinase  and  dias- 
tase. 

It  has  been  claimed  that  radium  emanation  is  of  value  in  all 
forms  of  non-suppurative,  acute,  subacute  and  chronic  arthritis 
(luetic  and  tuberculous  excepted),  in  chronic  muscle  and  joint  rheu- 
matism (so-called),  in  arthritis  deformans,  in  acute  and  chronic 
gout,  in  neuralgia,  sciatica,  lumbago,  and  in  tabes  dorsalis  for  the 
relief  of  lancinating  pains.    Its  chief  value  is  in  the  relief  of  pain. 

Surgical  Use:  The  efficiency  of  the  treatment  is  due  to  the  beta 
and  gamma  rays.  The  quantity  of  ray  is  proportional  to  the  amount 
of  radium  element  represented  in  the  salt  or  the  emanation.  Pure 
gamma  rays  may  be  employed  when  the  apparatus  is  surrounded  by 
at  least  3  mm.  of  lead.  Nearly  all  pathologic  tissues  are  more  sensi- 
tive than  normal  tissues.  There  is,  however,  a  wide  variation  in 
the  normal  tissues ;  e.g.,  the  ovary  and  the  sexual  organs  are  very 
sensitive,  the  eye  and  nervous  tissues  very  unsensitive.  In  skin  dis- 
eases marked  results  are  obtained  with  epitheliomata,  birthmarks 
and  scars. 

Technic:  Usually  heavy  doses  with  epitheliomata,  light  doses 
with  other  conditions.  New  growths,  benign  and  malignant,  of  the 
pelvic  organs,  the  breast,  the  neck  and  other  parts  of  the  body 
have  been  most  favorably  influenced  in  some  cases.  The  growths  of 
the  mucous  membrane  of  the  mouth  are  quite  resistant.  There  is  a 
remarkable  sedative  effect  in  true  neuralgia,  as  well  as  those  due  to 
tumor  pressure.  The  dosage  for  internal  work  is  heavy,  "  hundreds 
of  milligrams,"  and  always  with  the  pure  gamma  rays.   The  technic 


Am.  Jour.  Pharm. ) 
|April,  1914.  J 


Current  Literature. 


193 


of  filtration,  of  length  of  application  and  of  amount  is  still  in  an 
experimental  stage. 

The  radium  salts  and  the  emanation  can  be  placed  in  any  sealed 
container,  but  preferably  in  glass. 

Dosage:  It  may  be  administered  as  baths,  by  subcutaneous  in- 
jection in  the  neighborhood  of  an  involved  joint  (0.25  to  0.5  micro- 
curie  in  1  or  2  c.c.  distilled  water),  by  local  application  as  com- 
presses (5-10  microcuries),  by  mouth  as  a  drink  cure  (in  increas- 
ing doses  of  from  1-10  to  10  microcuries  three  or  more  times  a  day), 
by  inhalation,  the  patient  for  two  hours  daily  remaining  in  the 
emanatorium,  which  contains  0.0025  to  0.25  (average  0.1)  micro- 
curie  per  liter  of  air. 

Radium  Chloride. 

Radium  chloride  is  the  anhydrous  radium  salt,  RaCl2,  of  hydro- 
chloric acid.  While  nearly  pure  radium  chloride,  containing  76.1  per 
cent,  radium  (Ra),  is  said  to  be  obtainable,  the  market  supply  is  a 
mixture  of  radium  chloride  and  barium  chloride  and  is  sold  on  the 
basis  of  its  radium  content. 

Actions  and  Uses:  See  Radium. 

Dosage:  See  Radium. 

Non-Proprietary  Preparation : 

Radium  Chloride,  Standard  Chemical  Co. — Radium  chloride  is 
supplied  in  the  form  of  a  mixture  of  radium  chloride  and  barium 
chloride  for  use  in  radium  baths,  radium  drinking-water  and  inhala- 
toriums.    It  is  sold  on  the  basis  of  its  radium  content. 

Manufactured  by  the  Standard  Chemical  Co.,  Pittsburgh,  Pa. 
(The  Radium  Chemical  Co.,  Pittsburgh,  Pa.). 

Pure  anhydrous  radium  chloride  occurs  as  a  white  or  slightly 
brownish  crystalline  substance,  soluble  in  water. 

The  presence  of  radium  can  qualitatively  be  demonstrated  by 
electroscopic  or  by  photographic  methods. 

The  quantitative  determination  of  radium  is  carried  out  accord- 
ing to  the  method  of  Rutherford  and  Boltwood  (Rutherford's 
"  Radioactive  Substances  and  their  Radiations  "). 

Radium  Sulphate. 

Radium  sulphate  is  the  anhydrous  radium  salt,  RaS04,  of  sul- 
phuric acid.  While  nearly  pure  radium  sulphate,  containing  70.2 
per  cent.  (Ra),  is  said  to  be  obtainable,  the  market  supply  is  a 


194 


Current  Literature. 


{Am.  Jour.  Pharni. 
u  April,  1914.  , 


mixture  of  radium  sulphate  and  barium  sulphate  and  is  sold  on  the 
basis  of  its  radium  content. 

Actions  and  Uses:  See  Radium. 

Dosage:  See  Radium. 

Non-Proprietary  Preparation : 

Radium  Sulphate,  Standard  Chemical  Co. — Radium  sulphate  sup- 
plied in  the  form  of  a  mixture  of  radium  sulphate  and  barium  sul- 
phate for  use  in  applicators.  It  is  sold  on  the  basis  of  its  radium 
content. 

Manufactured  by  the  Standard  Chemical  Co.,  Pittsburgh,  Pa. 
(The  Radium  Chemical  Co.,  Pittsburgh,  Pa.). 

Pure  radium  sulphate  occurs  as  a  white  substance  insoluble  in 
water  and  dilute  acids. 

The  presence  of  radium  may  be  qualitatively  determined  by 
electroscopic  or  by  photographic  means. 

The  radium  content  may  be  determined  as  in  the  case  of  radium 
chloride. 

Warning  to  Users  of  Turpentine  for  Medicinal  or 
Veterinary  Purposes. 

As  the  result  of  an  investigation  by  the  U.  S.  Department  of 
Agriculture,  it  has  been  found  that  the  adulteration  of  turpentine 
with  mineral  oils  is  so  widespread  that  druggists  and  manufacturers 
of  pharmaceutical  products  and  grocers'  sundries  should  exercise 
special  caution  in  purchasing  turpentine.  Those  who  use  turpentine 
for  medicinal  and  veterinary  purposes,  unless  they  are  careful, 
run  the  risk  of  obtaining  an  adulterated  article  and  unnecessarily 
laying  themselves  open  to  prosecution  under  the  Food  and  Drugs 
Act. 

It  has  been  found,  moreover,  that  the  turpentine  sold  to  the 
country  stores  especially,  as  usually  put  out  by  dealers  and  manu- 
facturers of  grocers'  sundries,  is  often  short  in  volume  by  as  much 
as  5  or  i o  per  cent.  Dealers,  therefore,  should  also  protect  them- 
selves through  a  guarantee  from  the  wholesaler  that  the  bottle  con- 
tains the  full  declared  volume. 

The  Department  has  found  that  turpentine  may  be  adulterated 
in  the  South  where  it  is  made  and  that  the  further  it  gets  from  the 
South  the  more  extensively  and  heavily  it  is  adulterated. 

In  all  cases,  druggists,  manufacturers  and  wholesale  grocers 
should  satisfy  themselves  that  the  turpentine  is  free  from  adultera- 
tion and  is  true  to  marked  volume. 


THE  AMEEICAN 


JOU 


OF  PHARMACY 


NOTES  ON 


ATION  OF  NITROGLYCERINE. 


By  F.  W.  Heyl  and  J.  F.  Staley. 


After  abandoning  the  older  nitrometer  method  for  the  control 
of  nitroglycerine  in  pharmaceutical  preparations,  it  was  the  practice 
in  this  laboratory  during  a  considerable  period  to  use  in  its  place 
the  modified  Kjeldahl  method  wherever  possible.  The  Kjeldahl 
method  was  found  to  give  results  in  this  instance  fully  as  reliable  as 
in  the  case  of  other  highly  nitrated  organic  substances  such  as 
picrates  and  picrolonates,  which  have  thus  been  successfully 
analyzed. 

Recently  the  latter  method  has  been  supplanted  in  this  laboratory 
by  that  introduced  by  Scoville,1  particularly  when  preparations  bear- 
ing minute  quantities  are  under  examination.  Before  abandoning 
the  Kjeldahl  method  for  the  superior  method  of  Scoville,  we  first 
compared  the  results  obtained  by  using  these  two  methods  in  the 
routine  analysis,  upon  various  samples  of  nitroglycerine  prepara- 
tions. In  view  of  the  comparatively  large  number  of  collaborators 
who  took  part  in  the  cooperative  work  recently  described  2  in  the 
annual  report  of  the  Official  Agricultural  Chemists,  the  results  here 
given  may  be  of  some  interest. 

In  this  valuable  bulletin  the  nitroglycerine  found  by  the  modified 
Scoville  method  is  compared  with  results  obtained  gravimetrically 
upon  the  same  sample  by  extracting  with  anhydrous  ether.  It  was 
the  experience  of  some  of  the  collaborators  that  the  gravimetric 

1Amer.  Jour.  Pharm.,  83,  359,  1911. 

2  Bureau  Chemistry  U.  S.  Dept.  Agric.  Bull.,  162,  214,  1912. 


(195) 


196  Notes  on  Estimation  of  Nitroglycerine.  { Al\fyU  ri»ularm' 

determination  of  nitroglycerine  was  inaccurate,  and  this  would  be 
even  more  liable  to  error  in  anything  but  the  simplest  preparations. 
It  is,  therefore,  of  interest  to  note  the  comparisons  here  given  of 
nitroglycerine  content  as  determined  by  the  Scoville  method  and  by 
the  modified  Kjeldahl. 

Scoville 3  has  already  briefly  compared  these  values  and  the 
figures  here  given  lead  to  the  same  conclusions  as  his,  i.e.,  that  the 
results  obtained  by  these  methods  are  quite  alike,  and  that  .the  varia- 
tions are  due  to  the  difficulties  of  the  methods. 

For  the  analysis  of  tablets  containing  minute  quantities  there 
can  be  little  doubt  that  the  colorimetric  method  is  both  the  easier 
and  the  more  accurate.  But  in  the  case  of  the  stock  preparations 
such  as  the  concentrated  alcoholic  solutions  and  triturations,  the 
larger  quantities  of  nitroglycerine  under  analysis  make  it  possible 
to  obtain  closely  agreeing  results  by  the  modified  Kjeldahl  method. 
The  manufacturing  processes  can  be  closely  controlled  when  the 
stock  substances  are  standardized  by  the  Kjeldahl  and  the  finished 
product  by  the  colorimetric  method,  particularly  when  the  condi- 
tions are  so  standardized  that  a  definitely  known  loss  of  nitro- 
glycerine, previously  determined,  is  allowed  for.  Such  data  are 
given  in  the  table. 

It  will  be  observed,  that  under  the  conditions  employed  for  man- 
ufacture, the  losses  of  nitroglycerine  involved  have  been  reduced  to 
quite  narrow  limits,  averaging  about  five  per  cent  for  moulded 
tablets  and  about  eleven  per  cent  for  compressed  ones.  Our  find- 
ings on  the  compressed  tablets  "are  at  variance  with  the  losses  pre- 
viously recorded  4 ;  but  this  is  due  to  the  fact  that  the  tablets  are  pre- 
pared by  mixing  dry  granulations  instead  of  attempting  to  granulate 
the  mixture.  A  tablet  prepared  in  this  way  neither  discolors  nor 
loses  its  strength,  and  there  is  no  doubt  but  that  a  stable  standard 
product  results,  at  least  as  long  as  the  preparation  is  properly  pre- 
served. 

Experimental. 

For  the  colorimetric  analyses  a  method  equivalent  to  that  out- 
lined in  the  report 5  of  the  Official  Agricultural  Chemists  was  em- 
ployed. 


3  Lor.  cit. 

4  Amee.  Jour.  Pharm.,  79,  555,  1907. 

5  hoc.  cit. 


Am'£y r 'lS11™' }  Notes  on  Estimation  of  Nitroglycerine.  197 

The  nitrogen  determinations  were  made  as  follows :  Approxi- 
mately one  gram  of  the  ten  per  cent  alcoholic  solution  was  used  for 
analysis.  Where  tablets  and  triturations  were  analyzed  they  were 
first  extracted  with  anhydrous  ether,  and  the  ether  extracts  were 
evaporated  to  dryness  under  reduced  pressure  at  room  temperature. 
The  residue  was  taken  up  in  1  to  2  c.c.  alcohol  and  collected  at  the 
bottom  of  the  flask.  Upon  this  alcoholic  solution  one  gram  of 
salicylic  acid  was  placed  and  then  the  Kjeldahl  flask  was  cooled  in  a 
freezing  mixture.  Upon  this  40  c.c.  of  the  customary  salicylic  acid 
in  sulphuric  acid  solution  (previously  chilled)  was  poured  and  then 
the  mixture  was  allowed  to  warm  to  room  temperature,  with  occa- 
sional agitation.  The  nitration  mixture  was  reduced  by  the  gradual 
addition  of  2  grams  of  zinc  dust,  and  then  the  reduction  was  com- 
pleted by  allowing  the  reaction  to  continue  for  six  hours.  The 
mixture  was  heated  gently  for  five  minutes,  ten  grams  of  potassium 
sulphate  was  added,  and  the  Kjeldahl  determination  was  then  finished 
in  the  usual  manner,  using  N/20  solutions. 

The  following  table  gives  the  results  of  analyses  on  tablets,  some 
prepared  experimentally  and  some  commercially: 


Preparation  analyzed. 


r.  Nitroglycerine  sol. . 

2.  Nitroglycerine  trit. 

3.  Compressed  tablets 

4.  Compressed  tablets 

5.  Compressed  tablets 

6.  Compressed  tablets 

7.  Compressed  tablets 

8.  Moulded  tablets. . . 

9.  Moulded  tablets. . . 
10.  Moulded  tablets. . . 

EX.  Moulded  tablets. . . 

12.  Moulded  tablets. . . 


Nitroglycerine 

calculated 
gm.  per  tablet. 


0. 0007744 

0. 0005194 

0. 0007732 

0. 0006234 

o. 0004015 

0. 0006493 

0. 000658 
,0. 00053S1 

0. 000720 
0. 000688 


Found 
Kjeldahl. 


9.83% 
9.65% 
9.66% 
9.82% 
9.56% 
-9.7i% 
9-99% 
9.63% 
0007228 
0007039 


0.0004557 
o. 0004768 
o. 0004546 
0.0007395 


o. 0005298 
o. 0005298 

0. 0003512 
o. 0003474 
o. 0006328 
o. 0006328 
o. 0006280 
0.0005237 


0. 000629 


Found 

Scoville.  per 


9.75% 
9-87% 


10.03% 
9-88% 


0. 0007044 
0. 0006843 
o. 0007083 
0. 0004540 
0. 0004508 

o. 0007038 
0. 0006967 
0. 0006850 
0.0005273 
0.0005559 

0.0005559 
o. 0003552 
o. 0003596 
o. 0006588 

0. 000616* 
o. 0005085 
o. 0005184 
0. 0006836 
o. 0006480 


*  This  analysis  was  made  three  months  after  the  Kjeldahl. 


198  Use  of  Antitoxins  and  Vaccines.       { Xmw™\$u&rrn' 

Since  the  losses  involved  in  the  manufacture  of  these  products 
must  vary  with  the  mechanical  details,  a  brief  description  of  the 
mechanical  conditions  employed  will  suffice.  The  compressed  tablets 
were  usually  made  in  unit  runs  of  50,000  and  the  calculated  strength 
in  the  table  was  found  by  taking  into  account  both  the  waste,  which 
was  in  each  case  weighed,  and  also  the  over  or  under  run  in  number. 
The  moulded  tablets  were  made  in  unit  batches  of  15,000  and  dried 
artificially  in  45  to  60  minutes.  All  the  calculations  of  loss  are  based 
on  the  colorimetric  determinations. 
Contribution  from  the  Chemical  Research 

Laboratory  of  The  Upjohn  Company. 
Kalamazoo,  Mich.,  March,  1914. 


THEORIES  UNDERLYING  THE  USE  OF  ANTITOXINS 
AND  VACCINES.* 
By  A.  Parker  Hitchens,  M.D.,  Glenolden,  Pa. 

The  action  of  antitoxins  has  so  definitely  passed  beyond  the 
stage  of  pure  speculation  that  I  think  there  will  be  little  difficulty  in 
expounding  the  theories  underlying  their  use.  With  regard  to 
vaccines  likewise  we  have  come  to  understand  more  clearly  their 
mode  of  action  without  the  use  of  a  terminology  recognized  only  by 
the  initiated  few. 

Out  of  studies  in  immunology — the  science  dealing  with  the 
mechanism  of  contagious  diseasea — have  developed  methods  by 
which  the  body  may  be  assisted  either  to  prevent  disease-producing 
germs  from  gaining  a  foothold,  or  to  eliminate  them  after  they 
have  become  established.  • 

The  disease-producing  bacteria  are  classified  in  various  ways, 
according  to  their  functions.  For  our  present  purpose,  the  classifica- 
tion of  most  interest  is  that  which  considers  the  bacteria  according 
to  their  manner  of  causing  disease.  Thus  we  find  that  one  group 
of  bacteria  produces  definite,  soluble,  and  diffusible  poisons,  and 
that  all  the  symptoms  of  the  disease  are  directly  or  indirectly  de- 
pendent on  the  action  of  these  poisons  upon  the  tissues  for  which 
they  have  an  affinity.  The  second  group  of  bacteria,  on  the  con- 
trary, does  not  produce  soluble  and  diffusible  toxins  in  appreciable 

*  Read  at  a  meeting  of  the  American  Pharmaceutical  Association,  Phila- 
delphia Branch,  April  7,  1914. 


AnaMJa°yUriyi4arm'}       ^sc  °f  Antitoxins  and  Vaccines.  199 

quantity — their  effect  is  brought  about  by  a  much  more  complicated 
process.  We  believe  the  production  of  disease  by  this  class  of 
bacteria  is  not  a  function  in  which  they  alone  participate,  but  is  the 
result  of  their  interaction  with  the  body  cells. 

Antitoxins. 

Belonging  to  the  first  class  of  bacteria,  the  only  organisms  of 
interest  to  us  are  the  diphtheria  bacillus  and  the  tetanus  bacillus. 
These  produce  soluble  and  diffusible  poisons — toxins;  and  spon- 
taneous recovery  from  these  diseases  depends  upon  the  generation 
by  the  tissues  of  a  substance  which  will  neutralize  the  toxins — 
antitoxins.  The  requisite  antitoxins  can  be  easily  produced  in 
animals  and  transferred  to  the  bodies  of  patients  by  administering 
the  blood  serum  of  the  treated  animals. 

For  obvious  reasons,  horses  are  generally  selected  for  the  pro- 
duction of  antitoxin.  The  germs  in  question  are  developed  upon  a 
fluid  artificial  culture  medium — veal  broth.  After  the  bacteria  are 
removed  from  the  full-grown  culture,  the  sterile  filtrate,  containing 
the  specific  toxins,  is  injected  subcutaneously  into  the  horses.  The 
horses  react  by  the  production  of  antitoxin.  Enormous  quantities 
of  toxin  are  administered,  and  consequently  enormous  quantities  of 
antitoxin  are  generated  and  stored  in  the  blood  serum  of  the 
animal.  The  antitoxins  on  the  market,  then,  consist  of  this  blood 
serum,  either  native  or  chemically  treated  so  that  the  pseudoglobulin 
constituent  of  horse  serum  which  carries  with  it  the  antitoxic 
principle  is  removed  and  furnished,  in  solution,  in  as  pure  a  state 
as  possible. 

The  strength  of  the  antitoxin  is  determined  by  titrating  it  against 
toxin,  the  guinea  pig  being  used  as  indicator.  In  defining  a  unit  at 
present,  there  is  no  more  reason  to  say  that  it  is  the  amount  that 
will  neutralize  200  fatal  guinea-pig  doses  of  a  theoretically  pure 
toxin  than  there  is,  in  defining  an  inch,  to  say  that  it  has  a  definite 
relation  to  the  circumference  of  the  earth.  Twelve  inches  make  1 
foot,  36  inches  1  yard ;  1000  units  of  diphtheria  antitoxin  constitute 
the  immunizing  dose,  5000  units  the  average  initial  curative  dose ; 
1500  units  is  the  official  immunizing  dose  of  tetanus  antitoxin. 

The  action  of  diphtheria  antitoxin  may  be  clearly  illustrated 
by  imagining  the  disease  to  be  due  to  a  mineral  acid  generated 
within  the  body  and  poured  into  the  circulation  in  constantly  in- 
creasing quantities.    According  to  the  urgency  of  the  case,  let  us 


200  Use  of  Antitoxins  and  Vaccines.       j Am •MJa°yur*19i^ arm' 

inject  a  corresponding  quantity  of  a  harmless  alkali.  The  acid  is 
neutralized,  the  disease  is  controlled,  and  the  fate  of  the  patient 
now  depends  only  upon  the  amount  of  damage  done  to  the  tissues 
before  the  alkali  was  administered. 

In  tetanus  the  case  is  slightly  different.  Tetanus  toxin  has  a 
strong  affinity  for  the  nerve  tissues,  and  the  compound  formed  by 
this  union  cannot  be  split  up  by  antitoxin.  After  symptoms  of  the 
disease  have  developed,  there  is  but  one  hope  in  treating  tetanus 
with  antitoxin.  If  treatment  has  begun  before  the  lethal  quantity 
of  toxin  has  been  fixed  by  the  nervous  tissue,  and  if  the  amount  of 
antitoxin  then  administered  be  sufficient  to  neutralize  the  free  toxin 
in  the  blood,  there  is  a  chance  that  recovery  may  ensue. 

Bacterial  Vaccines. 

For  a  clear  understanding  of  the  action  of  bacterial  vaccines, 
it  may  be  helpful  to  consider  this  subject  from  the  standpoint  of 
our  knowledge  of  anaphylaxis.  Anaphylaxis,  in  its  derivation, 
means  a  lack  of  resistance — it  is  the  opposite  of  prophylaxis.  Richet, 
in  his  investigation  of  certain  poisons  derived  from  sea  urchins, 
noted  that  an  injection  of  this  poison  into  a  dog,  instead  of  render- 
ing the  animal  immune  to  a  second  dose,  actually  made  him  more 
susceptible.  The  work  of  Rosenau  and  Anderson  showed  still  more 
clearly  the  operation  of  this  phenomenon. 

Anaphylaxis  concerns  the  effect  of  proteins  or  albuminous  sub- 
stances upon  animals ;  it  concerns  all  proteins,  whether  they  are 
poisonous  in  themselves  or  not ;  for  instance,  egg  white  and  normal 
horse  serum  act  precisely  as  the  proteins  of  the  plague  bacillus  or 
of  the  typhoid  bacillus.  And,  furthermore,  the  proteins  of  dead 
bacteria  act  practically  in  the  same  way  as  the  proteins  of  living 
bacteria.  It  must  be  remembered,  however,  that  anaphylactic 
symptoms  can  be  produced  only  by  proteins  foreign  to  the  animal ; 
that  is,  anaphylaxis  cannot  occur  in  a  guinea  pig  from  the  repeated 
injection  of  guinea-pig  serum,  nor  can  the  symptoms  be  produced 
in  a  horse  by  the  injection  of  horse  serum. 

If  we  inject  a  guinea  pig  parenterally — that  is,  by  any  route 
except  by  the  gastro-intestinal  canal — it  does  not  appear  to  suffer 
the  slightest  inconvenience.  If,  however,  we  inject  this  animal,  two 
or  more  weeks  later,  with  the  same  protein,  it  will  die  within  one 
or  two  minutes  and  with  very  definite  symptoms  accompanying 
death.    This  is  a  manifestation  of  anaphylaxis. 


Am'M^ri9i4 arm' }      Use  of  Antitoxins  and  Vaccines.  201 

For  an  explanation  of  this  phenomenon  we  must  go  back  to  the 
work  of  Prof.  Victor  C.  Vaughan  upon  the  chemistry  of  the 
protein  molecule.  Vaughan  has  shown  that  a  protein,  treated 
chemically  according  to  his  method,  is  split  into  two  parts — the  one 
poisonous,  the  other  non-poisonous.  The  poisonous  part  obtained 
from  all  proteins  is  the  same  whether  it  results  from  the  splitting 
of  egg  white  or  from  the  splitting  of  typhoid  bacilli;  the  symptoms 
leading  to  death  in  the  guinea  pig  are  identical.  This  poisonous 
part,  then,  is  a  poison  and  has  no  other  function  or  effect ;  one  dose 
has  no  bearing  upon  the  effect  of  a  subsequent  dose,  no  hyper- 
susceptibility  is  produced,  and  no  tolerance,  even  by  repeated 
administration. 

The  non-poisonous  part,  on  the  other  hand,  is  specific  in  its 
action.  The  non-poisonous  part  of  typhoid  bacillus  protein  will 
immunize  an  animal  against  typhoid  infection,  but  not  against 
infection  with  colon  bacilli ;  the  non-poisonous  part  of  horse  serum 
will  sensitize  a  guinea  pig  to  horse  serum,  but  not  to  goat  or 
sheep  serum. 

These  results  of  Vaughan's  work  upon  the  chemistry  of  proteins 
suggest  an  explanation  of  the  mechanism  of  anaphylaxis ;  they  show 
us  that,  instead  of  being  the  opposite  of  immunity,  anaphylaxis  is 
merely  one  of  its  manifestations ;  and,  furthermore,  they  give  us  a 
clearer  understanding  of  immunity  itself. 

When  foreign  proteins  are  injected  into  the  tissues  of  an  animal, 
the  body  cells  at  once  set  to  work  to  remove  this  protein.  They 
prepare  a  ferment  capable  of  splitting  the  protein  molecule,  which 
possibly  because  of  its  size  is  not  diffusible,  into  smaller  fractions 
able  to  pass  into  the  circulatory  system  and  be  thence  eliminated. 
These  fractions  of  the  protein  molecule  are  similar  to  those  ob- 
tained by  Vaughan  in  his  chemical  splitting;  that  is,  a  poisonous 
part  which,  after  the  first  injection,  is  liberated  slowly  and  is  there- 
fore harmless  in  its  effect,  and  a  non-poisonous  specific  part  which 
stimulates  the  body  cells  to  produce  a  specific  ferment-like  sub- 
stance. About  two  weeks  after  injection  the  protein  has  been 
entirely  removed  from  the  tissues,  the  poisonous  part  has  been 
eliminated  so  gradually  that  no  symptoms  have  resulted,  and  the 
non-poisonous  part  has  stimulated  the  tissues  to  generate  a  large 
amount  of  specific  protein-splitting  ferment. 

At  this  point  we  must  pause  to  note  that,  according  to  Vaughan, 
the  protein-splitting  ferment  includes  the  antibodies  so  difficult  to 


202 


Use  of  Antitoxins  and  Vaccines. 


Am.  Jour.  Pharm. 
May,  1914. 


understand  in  the  theories  of  the  German  and  French  schools  of 
immunity.  This  theory  of  the  American  school  does' not  contradict 
the  fact  established  by  Metchnikoff,  and  further  elucidated  by 
Wright,  that  the  white  blood-corpuscles  play  an  active  part  in 
the  removal  of  foreign  proteins,  whether  they  be  cells  or  fluids; 
nor  is  it  out  of  harmony  with  the  theory  of  Ehrlich,  who 
gives  to  the  group  of  antibodies — collectively  called  "  the  ferment  " 
by  Vaughan — different  names  according  to  their  functions. 

The  guinea  pig,  then,  at  the  end  of  two  weeks  after  the  first 
injection  of,  let  us  say,  horse  serum  contains  in  his  tissues  no  trace 
of  horse  serum ;  but  he  does  have  within  his  body  a  large  quantity 
of  protein-splitting  ferment  which  may  remain  in  the  tissues  for  a 
long  time ;  and,  even  if  it  disappears,  the  power  to  generate  this 
ferment  upon  demand  may  remain  permanently.  If  we  now  inject 
into  this  guinea  pig  a  second  dose  of  horse  serum,  the  proteins 
contained  therein  are  at  once  attacked  by  the  specific  ferment ; 
digestion  occurs  almost  immediately,  resulting  in  the  liberation 
of  a  large  quantity  of  the  poisonous  part  of  the  protein  molecule ; 
the  animal  is  overwhelmed  by  it  and  dies  usually  in  less  than  five 
minutes.  A  dose  sufficiently  large  to  cause  death  depends  upon  the 
method  of  injection;  if  injected  into  the  circulation  or  into  the 
brain,  1/20  ex.  is  sufficient;  if  injected  subcutaneously,  however,  at 
least  5  c.c.  is  usually  necessary. 

Now  as  to  the  bearing  of  this"  phenomenon  upon  infectious 
disease — Vaughan  has  used  typhoid  fever  as  a  typical  illustration. 
Infection  results  from  the  entrance  of  a  few  typhoid  bacilli  into 
the  tissues  under  circumstances  which  permit  their  growth  and 
multiplication.  There  is  normally  present  in  the  body  a  small 
amount  of  a  non-specific  protein-splitting  ferment  which  attacks 
the  typhoid  bacilli,  liberating  the  non-poisonous  part,  which  in  turn 
begins  to  stimulate  the  tissues  to  the  production  of  a  specific  anti- 
typhoid ferment.  We  know  that  in  guinea  pigs  it  takes  from  eight 
to  fourteen  days  to  produce  enough  ferment  to  cause  serious 
symptoms  of  intoxication  upon  the  injection  of  a  second  dose  of  the 
protein.  Now  this  period  corresponds  exactly  to  the  incubation 
period  in  typhoid  fever.  It  is  during  this  time  that  the  typhoid 
protein-splitting  ferment  is  produced  in  increasing  quantities,  while 
the  typhoid  bacilli  are  rapidly  growing  in  numbers.  The  ferment 
sets  free  the  poisonous  part  in  gradually  increasing  quantities  with 
the  final  appearance  and  progressive  increase  of  fever  and  the  other 


Am'Mayr'iw4arm'}       ^  se  °f  Antitoxins  and  Vaccines.  203 

symptoms  of  the  disease.  This  process  continues  up  to  the  point 
where  the  number  of  typhoid  .bacilli  destroyed  each  day  equals  the 
number  reproduced  in  the  lesion.  This  balance  is  maintained  for  a 
time  until  the  number  of  bacilli  destroyed  exceeds  those  reproduced. 

A  patient  recovered  from  typhoid  fever  has  remaining  in  his 
tissues  a  large  amount  of  typhoid  protein-splitting  ferment,  so  that 
when  typhoid  bacilli  again  gain  entrance  to  his  tissues  they  are  at 
once  attacked  and  destroyed  before  they  have  a  chance  to  develop. 
Obviously  there  is  no  intoxication,  because  the  amount  of  typhoid 
proteins  is  infinitesimal  compared  to  the  amount  necessary  to  result 
in  anaphylactic  shock. 

It  is  now  easy  to  understand  the  action  of  typhoid  vaccine. 
When  we  inject  beneath  the  skin  a  number  of  typhoid  bacilli,  their 
disintegration  is  started  by  the  normal  proteolytic  ferments  in  the 
body.  A  second  and  third  dose  given  at  intervals  of  about  ten  days 
increases  the  quantity  of  specific  typhoid  protein-splitting  ferment. 
The  theory  of  typhoid  immunity  by  means  of  bacterial  vaccines 
applies  equally  to  the  production  of  immunity  to  other  infecting 
bacteria.  The  theory  underlying  the  use  of  bacterial  vaccines  in 
disease  is  based  on  the  fact  that  the  tissues  affected  are  unable  to 
produce  a  sufficient  quantity  of  the  specific  ferment  to  overcome 
the  infection.  The  injection  of  bacterial  proteins  in  a  healthy  part 
of  the  body  leads  to  the  production  there  of  these  antibodies,  which 
are  conveyed  to  the  focus  of  infection  through  the  circulatory  system 
and  thus  assist  the  local  cells. 

It  will  now  be  clear  that  the  requisites  to  success  in  vaccine 
therapy  are  (1)  that  the  vaccine  injected  must  contain  bacterial 
proteins  identical  in  kind  with  those  causing  the  infection,  (2) 
that  the  ferment  produced  locally  must  come  in  contact  with  the 
infecting  bacteria.  For  one  with  proper  training  it  is  not  hard 
to  determine  the  kind  of  bacteria  causing  an  infection  ;  nor  is  it  hard 
to  obtain  either  a  stock  vaccine  representing  these  bacteria  or  to 
prepare  an  autogenous  vaccine  identical  with  them ;  and  it  is  a 
very  simple  matter  to  inject  these  bacterial  suspensions  beneath 
the  skin  of  the  patient. 

If  the  patient  is  not  in  the  last  stages  of  disease,  there  is  not  one 
chance  in  many  thousands  that  his  tissues  will  fail  to  produce  the 
proper  antibodies  or  ferments.  If  the  patient  shows  no  improve- 
ment as  result  of  the  treatment,  it  behooves  the  physician  to  use 
means  by  which  the  ferments  may  be  induced  to  perform  their 
function. 


204  Use  of  Antitoxins  and  Vaccines.      { Am"Ma°y  r'i9u arm" 

In  some  infections,  as  in  staphylococcic  infection,  accessory 
measures  are  seldom  needed,  while  in  streptococcic  infections  they 
are  nearly  always  necessary.  In  gonococcic  infections  of  the  urethra 
and  prostate,  the  mere  injection  of  vaccines  accomplishes  but  little; 
in  gonococcic  infections  of  the  joints,  however,  the  vaccine  is 
apparently  sufficient. 

We  are  indebted  to  Besredka  of  the  Pasteur  Institute  in  Paris 
for  an  improvement  upon  bacterial  vaccines  which  constitutes  a 
real  advance  in  vaccine  therapy.  As  said  above,  when  the  bacterial 
vaccine  is  injected  beneath  the  skin  a  small  quantity  of  the  protein 
is  split  up  by  natural  ferments  and  the  specific  non-poisonous  part 
thus  liberated  stimulates  the  production  of  ferments  which  con- 
tinue the  disintegration  until  the  maximum  effect  of  the  vaccine 
is  obtained. 

The  ferment  itself  is  composed  of  at  least  two  constituents;  one 
is  specific,  and  by  Ehrlich  has  been  called  amboceptor  (the  opsonin 
of  Wright  is  a  similar  antibody).  This  substance  has  the  power 
of  fixing  itself  to  the  bacteria,  thus  preparing  them  for  digestion 
by  another  substance  which  is  not  specific  but  is  always  present 
in  the  blood  of  healthy  animals,  and  because  the  latter  completes 
the  ferment  action  it  is  called  complement.  Besredka  proposed 
that  amboceptor  be  utilized  to  prepare  the  bacteria  for  the  immediate 
action  of  the  complement.  The  amboceptor  is  obtained  by  injecting 
goats  or  sheep  with  massive  doses  of  bacteria  like  those  it  is  desired 
to  sensitize.  Bacteria  thus  prepared  for  the  action  of  the  com- 
plement were  said  to  be  "  sensitized,"  and  the  suspensions  of  such 
bacteria  were  called  by  him  "  sensitized  vaccines."  The  advantage 
they  have  over  ordinary  bacterial  suspensions  is  that  they  eliminate 
the  period  during  which  the  specific  ferment  is  being  formed. 
"  Sensitized  vaccines  "  have  already  been  used  extensively  in  France 
and  also  to  a  certain  extent  in  England.  The  published  reports 
amply  attest  their  superiority. 


Antibacterial  Serums. 


The  so-called  "  therapeutic  or  antibacterial  serums "  include 
antistreptococcic,  antipneumococcic,  and  antimeningococcic  serums. 
These  are  prepared  by  the  injection  of  horses  first  with  dead  and 
then  with  living  bacteria.  In  the  case  of  antimeningococcic  serum 
injections  of  autolyzed  bacteria  are  alternated  with  the  cocci  them- 


^  May  ri9i4arm* }       Use  °f  Antitoxins  and  Vaccines.  205 

selves.  The  autolysate  contains  a  toxic  substance  which  causes 
the  production  of  some  antitoxin.  This  serum,  like  antidysenteric 
serum,  partakes,  therefore,  of  the  nature  of  both  an  antitoxic  and 
an  antibacterial  serum. 

These  serums  depend  for  their  activity  upon  substances  called 
ferments  by  Vaughan,  but,  according  to  the  nomenclature  of  Ehrlich, 
"  antibodies  " ;  that  is,  substances  antagonistic  to  the  bacteria.  Used 
in  sufficiently  large  doses,  antibacterial  serums  have  undoubtedly 
great  value.  The  chief  difficulty  lies  in  the  fact  that  no  method 
has  so  far  been  found  by  which  antibacterial  serums  can  be  pro- 
duced comparable  in  potency  with  diphtheria  antitoxin. 

It  is  well  known  that  a  much  larger  dose  of  any  curative  serum 
must  be  used  if  it  is  injected  subcutaneously  than  if  injected  intra- 
venously. Realizing  this  fact  and  the  relative  weakness  of  anti- 
bacterial serums,  there  is  but  little  doubt  that  their  use  intravenously 
will  be  resorted  to  in  the  future  with  increasing  frequency. 

Summary. 

1.  There  are  two  classes  of  bacteria  with  regard  to  their  method 
of  producing  disease:  (a)  Those  that  produce  soluble  and  diffusible 
toxins,  and  (b)  those  that  do  not. 

2.  The  toxin-producing  bacteria  are  the  diphtheria  bacillus  and 
the  tetanus  bacillus. 

3.  Antitoxins  produced  by  injecting  horses  with  the  specific 
toxins  are  antagonistic  to  the  specific  toxic  products  of  the  bacilli 
in  a  manner  very  similar  to  the  antagonism  between  acid  and  alkali. 

4.  To  the  second  class  belong  the  great  majority  of  the  disease- 
producing  bacteria. 

5.  The  symptoms  in  the  diseases  caused  by  the  latter  are  prob- 
ably the  result  of  the  action  of  their  specific  metabolic  products 
combined  with  the  effect  of  the  liberated  poisonous  part  of  their 
protein  molecule. 

6.  Recovery  from  such  infectious  diseases  depends  upon  the 
production  of  sufficient  specific  protein-splitting  ferment  to  remove 
their  causative  bacteria  from  the  tissues. 

7.  The  amount  of  this  specific  protein-splitting  ferment  may  be 
increased  by  injecting  bacteria  of  the  same  kind  beneath  the  healthy 
skin. 

8.  Immunity  from  infectious  disease  depends  upon  the  existence 


2C>6 


Autogenous  Vaccines. 


Am.  Jour.  Pharm, 
May,  19U. 


in  the  tissues  of  sufficient  specific  protein-splitting  ferment  to  dis- 
solve invading  bacteria  before  they  have  a  chance  to  develop. 

9.  The  rational  administration  of  bacterial  vaccines  presupposes 
accurate  diagnosis  and  the  administration  of  bacteria  identical  in 
kind  with  those  causing  the  infection.  It  depends,  furthermore, 
upon  the  ability  of  ferments  and  antibodies  to  come  in  contact  with 
the  infecting  bacteria. 

10.  "  Sensitized  vaccines "  are  superior  to  ordinary  vaccines 
because  they  reduce  the  preliminary  period  during  which  the  in- 
jected bacteria  are  being  split  up  so  that  the  non-poisonous  part  may 
be  available  for  the  production  of  specific  antibodies. 

11.  Antibacterial  serums — antistreptococcic  and  antipneumo- 
coccic — depend  for  their  activity  upon  their  content  in  specific  anti- 
bodies or  ferments. 

12.  The  amount  of  these  ferments  in  even  the  best  serums  is 
relatively  small,  and  the  serums  must  therefore  be  used  in  larger 
doses  than  has  been  customary  in  the  past. 

13.  Antimeningococcic  serum  is  both  antibacterial  and  anti- 
toxic. 

14.  Since  the  efficiency  of  curative  serums  is  increased  many 
fold  when  administered  intravenously,  this  route  will  be  used  more 
frequently  than  has  been  the  custom  in  the  past. 


A  CONSIDERATION  OF  AUTOGENOUS  VACCINES. 

By  B.  B.  Vincent  Lyon,  A.B.,  M.D. 
Pathologist  to  Methodist  Episcopal  Hospital;  Assistant  Pathologist  to  German 

Hospital,  Philadelphia. 

Empiricism  is  dying.  Throughout  the  last  century,  and  par- 
ticularly its  latter  decades,  the  searchlight  of  truth  has  lighted  up 
many  of  the  heretofore  dark  places  in  the  study  and  practice  of 
medicine.  The  discovery  of  the  causation  of  many  diseases  through 
bacterial  agencies  was  epoch-making,  and  led  the  way  naturally 
toward  the  introduction  of  measures  able  to  cope  with  such  a  foe. 

During  the  last  thirty  years  scores  of  men  have  been  at  work  on 
this  problem  and  have  each  added  their  little  to  the  sum  of  our 
present  knowledge,  and  from  the  time  of  Jenner  one  startling 
etiologic  and  therapeutic  discovery  has  followed  another,  so  that 
among  the  names  destined  to  live  will  always  be  found  those  of 


Am.  Jour.  Pharm. 

May,  1914. 


Autogenous  Vaccines. 


207 


Pasteur,  Koch,  Pfeiffer,  Ehrlich,  Behring,  Wassermann,  Noguchi, 
and  others. 

Bacteria  are  divided  into  two  classes,  the  good  and  the  bad: 
saprophytic  and  pathogenic.  The  saprophytic  bacteria  are  scav- 
engers; they  thrive  best  on  dead  tissues  and  assist  in  freeing  the 
body  of  many  waste  products.  Pathogenic  bacteria  thrive  best  on 
the  living  tissues  of  the  host,  in  whom  they  are  capable  of  producing 
disease.  Their  pathogenic  action  is  due  to  the  liberation  of  the 
toxins  they  contain  or  the  elaboration  of  poisons  in  the  tissues 
of  the  host. 

Of  these  bacterial  toxins  there  are  two  main  types:  The  exo- 
toxins, contained  in  bacteria  whose  poisonous  principles  are  capable 
of  being  dissolved  out  of  the  bacterial  cell.  To  this  class  belong  the 
bacillus  of  diphtheria  and  the  bacillus  of  tetanus.  The  great  ma- 
jority of  bacteria,  however,  produce  endotoxins,  or  poisons  which 
are  incapable  of  separation  from  the  cell  bodies  by  any  of  our 
known  filtration  methods.  Examples  of  this  are  the  bacillus  of 
typhoid  fever  and  the  streptococcic  and  staphylococcic  groups,  etc. 

While  bacteria  are  capable  of  producing  disease,  it  is  not  through 
their  mere  presence  per  se,  for,  as  we  know,  our  persons  in  health 
permit  of  the  culturization  of  numerous  pathogenic  bacteria,  there- 
fore other  factors  must  enter  in,  and  these  factors  comprise  the 
natural  defensive  mechanism  of  the  body  against  disease. 

Natural  Resistance. — This  varies  greatly  with  the  individual 
and  has  a  certain  selective  action,  for  why  is  it  that  one  person 
can  harbor  in  his  mouth  virulent  pneumococci  and  streptococci  and 
yet  can  go  through  life  without  a  single  attack  of  pneumonia,  and, 
conversely,  be  subject  to  repeated  attacks  of  tonsillitis ;  whereas, 
another  individual  harboring  the  same  organisms  may  have  several 
attacks  of  pneumonia  during  his  lifetime,  and  none  of  tonsillitis. 
This  is  due  to  the  development  of  what  we  call  immunity,  which  is 
the  power  of  resistance  the  body  tissues  are  able  to  exert  against 
bacterial  poisons.  Immunity  may  be  divided  into  species  and  racial 
immunity. 

Species  Immunity. — It  is  well  known  that  many  animals  are 
naturally  immune  to  diseases  common  to  man,  and  that  it  is  only 
with  the  greatest  experimental  difficulties  that  infections  with  those 
diseases  can  be  made  successfully. 

Racial  Immunity. — Also,  among  the  different  races  of  the  same 
species  there  appears  to  be  a  natural  immunity  against  certain 


208 


Autogenous  Vaccines. 


Am.  Jour.  Pharm. 
May,  1914. 


diseases,  which  have  long  been  prevalent  in  that  particular  section, 
but  which  when  carried  to  another  section  where  fresh  soil  is 
obtained  immediately  light  up  into  virulent  epidemics.  This  is  seen 
in  the  ravages  of  tuberculosis  among  the  negroes  and  American 
Indians,  and  it  is  seen  conversely  in  the  immunity  from  yellow 
fever  that  has  long  been  enjoyed  by  the  negro. 

Acquired  immunity  is  the  protection  that  is  afforded  an  in- 
dividual who  has  passed  through  an  attack  of  one  disease,  this  con- 
ferring a  greater  resistance  to  that  disease  in  the  future.  This  is 
commonly  observed  in  diseases  like  typhoid  and  yellow  fever.  Ac- 
quired immunity  may  be  either  active  or  passive.  "  The  process 
of  conferring  protection  by  treatment  with  either  an  attenuated 
form  or  a  sublethal  quantity  of  the  infectious  agent  of  a  disease  or 
its  products  is  spoken  of  as  active  immunization,"  because  the 
immunized  individuals  gain  their  power  of  resistance  by  taking 
an  active  physiological  part  in  the  acquisition  of  this  new  property 
of  immunity.  Thus  active  immunity  can  be  acquired  by  repeated 
injections  of  attenuated  cultures,  as  in  Pasteur's  work  in  hog 
cholera;  by  injections  of  sublethal  doses  of  virulent  bacteria,  as 
demonstrated  in  the  protozoon  disease  of  Texas  fever;  by  injections 
of  killed  bacteria,  first  suggested  by  Chauveau.  This  method  of 
active  immunization  with  gradually  increasing  doses  of  killed  bac- 
teria has  been  carried  out  successfully  against  many  bacterial 
diseases.  It  is  particularly  useful  against  those  groups  of  bacteria 
producing  endotoxin;  and,  finally,  by  injections  with  bacterial 
products  from  poisons  excreted  or  liberated  from  the  bacterial  cell 
body.    These  measures  comprise  vaccination. 

Passive  immunity,  on  the  contrary,  is  that  gained  by  the  host 
through  no  active  formation  of  antibodies  on  its  own  part,  but 
rather  accepting  ready  to  hand  the  antibodies  prepared  by  the 
tissues  of  another  species.  The  most  conspicuous  types  of  this  are 
the  antidiphtheritic  and  antitetanic  sera.  These  are  both  designed 
to  meet  bacterial  exotoxins,  and  it  is  this  type  of  sera  that  is  most 
successful.  On  the  contrary,  antigonococcic,  antistreptococcic  sera, 
and  the  like,  which  depend  for  their  activity  on  the  lysin,  opsonin, 
and  other  antibodies  they  contain,  are  not  blessed  with  a  like  thera- 
peutic success.  Allen  states  that  "  these  sera  are  not  always  cura- 
tive ;  indeed,  their  use  during  active  disease  may  not  be  altogether 
free  from  danger.  Thus  the  administration  of  anticholera  or  anti- 
typhoid serum,  which  each  depend  for  their  activity  on  the  lysin 


Am.  Jour.  Phann. 
May,  1914. 


Autogenous  Vaccines. 


209 


they  contain,  may  result  in  the  extraleucocytic  lysis  of  so  many 
bacteria  that  the  resultant  flooding  of  the  tissues  with  large  quan- 
tities of  their  contained  endotoxin  may  imperil  the  life  of  the 
recipient  from  the  additional  toxaemia." 

Bacteria  have  a  selective  action :  not  only  must  they  gain  access 
to  the  body  in  large  enough  numbers  and  possessing  sufficient 
virulence,  but  they  must  also  gain  entrance  to  a  tissue  that  is  suit- 
able for  their  further  development.  For  instance,  you  can  rub  a 
typhoid  culture  into  an  abraded  surface  of  the  arm  or  a  culture 
of  streptococci  can  be  swallowed,  both  with  equal  impunity,  but 
reversing  the  conditions  a  bacterial  infection  is  sure  to  follow. 

Now  what  are  the  general  defences  of  the  body  against  this 
bacterial  invasion  ?    They  are  fourfold  : 

1.  Antitoxin,  a  substance  manufactured  by  the  tissues  which 
is  capable  of  neutralizing  the  soluble  toxins  produced  by  certain 
groups  of  bacteria. 

2.  Agglutinin,  a  substance  which  causes  bacteria  free  in  the 
tissues  or  blood  stream  to  be  clumped  together  in  masses  and  held 
nearly  immovable  and  therefore  more  accessible  for  phagocytosis. 
This  is  the  more  conspicuous  where  it  concerns  the  motile  bacteria. 
Though  originally  observed  in  1889  by  Charrin  and  Rogers,  in 
studying  the  Bacillus  pyocyaneus,  the  agglutination  reaction  is  com- 
monly associated  with  Widal,  who  first  applied  the  phenomenon  in 
the  diagnosis  of  disease  by  an  unknown  organism. 

3.  Lysin,  a  substance  or  substances  elaborated  by  the  body  which 
has  the  property  of  dissolving  certain  bacteria.  PfeifTer  noted  that 
guinea  pigs  which  had  been  immunized  against  cholera  bacilli  could 
withstand  the  further  intra-peritoneal  injection  of  virulent  cultures 
without  harm,  and  found  that  the  peritoneal  fluids  dissolved  the 
organisms. 

4.  Opsonin,  discovered  and  named  by  Wright,  is  a  substance  that 
prepares  or  sensitizes  the  bacteria  for  ingestion  by  the  phagocytic 
elements  of  the  white  blood-corpuscles. 

There  are  two  types  of  bacterial  infection :  local  and  general. 
The  former  is  best  represented  by  boils ;  the  latter  is  seen  in  diseases 
like  typhoid  fever,  pneumonia,  puerperal  sepsis,  and  the  like.  When 
a  person  recovers  from  a  bacterial  disease  like  typhoid  fever,  it  is 
by  the  body  having  gradually  elaborated  the  foregoing  antitoxins, 
agglutinins,  lysins,  and  opsonins  in  amounts  sufficient  to  cause  the 
neutralization,  destruction,  and  solution  of  the  bacteria.    The  time 


210 


Autogenous  Vaccines. 


(Am.  Jour.  Pharm. 
\       May,  1914. 


required  in  the  manufacture  of  these  substances  varies  in  different 
diseases:  21  to  28  days,  as  a  rule,  in  typhoid  fever;  9  to  11  days, 
as  a  rule,  in  pneumonia,  etc.  So  we  have  two  biologic  methods  of 
treatment,  serum  and  vaccine  treatment,  and  the  principle  of  the 
former  is  to  supply  these  protective  substances  ready  made  (passive 
immunity)  and  in  vaccination  to  stimulate  the  tissues  to  produce 
them  more  quickly,  and,  inasmuch  as  diseased  tissues  are  more 
sluggish  in  locally  manufacturing  them,  to  utilize  or  exploit  healthy 
tissues  for  the  advantage  of  the  enfeebled  ones  (active  immunity). 
This,  then,  is  the  scientific  basis  for  the  action  of  vaccines.  And  now 
what  are  vaccines? 

Vaccines  are  emulsions  of  the  bodies  of  dead  bacteria  killed  in 
various  ways  and  suspended  in  suitable  dosage  in  solution  of  nor- 
mal saline. 

There  are  two  types  of  vaccines :  heterogenous  and  autogenous. 
Heterogenous  vaccines  are  prepared  from  infections  similar  to  the 
case  which  is  to  be  treated,  but  from  infected  material  not  derived 
from  the  patient  himself.  This  type  of  vaccine  may  be,  and  usually 
is,  polyvalent;  that  is,  cultures  are  obtained  from  several  infections 
of  the  same  nature  and  therefore  represent,  possibly,  several 
"  strains  "  of  the  same  organism.  These  heterogenous  vaccines  are 
commonly  called  "  stock  "  vaccines,  perhaps  because  they  are  pre- 
pared in  quantities  and  held  in  readiness  to  be  used  in  a  given  case 
on  demand.  i  • '        H  L    j  i 

:  !-''■    '  !     ;  Li!;  m  I  1 

Autogenous  vaccines  are  prepared  from  cultures  grown  from  in- 
fected material  obtained  from  the  patient  himself.  In  other  words, 
they  represent  and  are  specifically  the  organism  from  the  effects  of 
which  the  patient  is  suffering  and  toward  which  you  are  assisting 
the  patient  to  establish  an  immunity.  Knowing  these  differences, 
it  is  not  difficult  to  understand  that  biologists,  bacteriologists,  se- 
rologists,  and  clinicians  of  the  thinking  type  are  agreed  that  the 
autogenous  group  of  vaccines  fulfil  best  the  scientific  therapeutic 
requirements.  Let  me  quote  from  an  article  recently  published 
by  a  man  whose  authority  is  unquestioned :  "  With  the  exception 
of  certain  organisms,  such  as  tubercle  bacillus  and  the  gonococcus, 
there  is  little  reason  for  employing  stock  vaccines  instead  of  au- 
togenous, and  there  is  abundant  ground  for  believing  that  the  use 
of  stock  vaccines  will  not  only  lead  to  carelessness  of  diagnosis  and 
misinterpretation  of  the  probable  nature  of  the  infection  with  con- 
sequent administration  of  the  wrong  species,  but  will  sometimes 
be  directly  harmful. 


Am.  Jour.  Pharm. 
May,  1914. 


Autogenous  Vaccines. 


211 


"  I  am  well  aware  that  the  argument  has  been  advanced  that 
laboratories  are  not  sufficiently-  available  to  practitioners  in  all  sec- 
tions to  make  it  possible  for  them  to  obtain  autogenous  vaccines, 
and  would  reply  that  in  a  measure  this  may  sometimes  be  true;  but 
the  general  demand  for  stock  vaccines  has  been  artificially  stimulated 
by  manufacturers,  and  the  practical  application  of  this  method  of 
treatment  has  outdistanced  the  scientific  investigation  of  its  merits. 
Instead  of  wholesome  growth  with  the  gradual  provisions  of  local 
agencies  where  autogenous  vaccines  could  be  obtained,  an  unwhole- 
some growth  of  this  mode  of  treatment  has  been  stimulated, 
and  those  who  seek  to  keep  up  with  the  latest  pronouncement  of 
advertisement  literature  find  themselves  in  a  position  of  dependence 
upon  stock  vaccines  in  many  cases.  There  can  be  no  doubt  that  in 
some  instances  stock  vaccines  are  satisfactory.  Staphylococcus 
and  typhoid  ,  and  tuberculosis  vaccine  are  instances,  but  the  other 
forms,  and  especially  streptococcus  and  pneumococcus  and  mixed 
vaccines,  are  of  very  doubtful  efficacy. 

"  Here  we  come  upon  the  field  of  variability  in  the  organisms 
themselves,  and,  unless  a  growth  has  been  prepared  from  the 
patient  himself,  the  strain  may  be  entirely  different  and  inappro- 
priate. It  avails  little  to  use  mixed  strains  which  require  the  reduc- 
tion of  dosage  of  the  one  possibly  present  and  available  strain 
below  the  point  of  usefulness  because  of  the  simultaneous  injection 
of  several  other  strains  in  the  mixture  which  are  of  no  use,  or 
practically  useless. 

"  As  for  stock  mixture  of  heterogenous  organisms  designed 
for  the  treatment  of  cases  in  which  no  sort  of  accurate  bacterio- 
logical diagnosis  has  been  made,  too  vigorous  condemnation  cannot 
be  phrased." 

In  my  own  personal  experience  I  have  met  with  many  cases 
referred  to  me  by  other  practitioners,  cases  on  whom  various 
■  stock  vaccines  had  been  tried  for  various  lengths  of  time,  in  various 
dosages,  with  absolutely  no  improvement,  and  which  have  responded 
with  surprising  promptness  to  an  autogenous  vaccine,  and  have 
established  an  immunity  that  in  many  cases  has  lasted  for  years, 
and  I  personally  have  used  in  some  cases  stock  vaccines  of  different 
types,  giving  them  a  thorough  trial,  only  to  become  discouraged  at 
their  non-success,  and  have  discarded  them  in  given  cases  for 
autogenous  vaccines  with  gratifying  results. 

On  the  other  hand,  I  believe  that  stock  vaccines  of  a  single 


212 


Autogenous  Vaccines. 


Am.  Jour.  Pharm. 
May,  1914. 


or  of  a  polyvalent  single  organism  type  have  their  place,  and  a  very 
important  place  of  usefulness,  in  the  48-96  hour  interval  that  is 
often  necessary  to  prepare  the  autogenous  vaccine,  after  the  bac- 
terial identification  in  the  specific  case  has  been  established,  and  I 
almost  uniformly  use  this  period  to  give  one  and  sometimes  two 
injections  of  the  appropriate  stock  culture.  Appropriate  stock 
cultures  may  often  be  used  with  value  in  association  with  autogenous 
vaccines  in  selected  cases. 

A  word  or  two  now  to  ensure  success  in  getting  the  proper 
bacterial  results  in  culture  taking.  The  first  principle  is  to  obtain 
your  material  free  from  contamination,  and  this  requires  the  observ- 
ance of  special  precautions  according  to  the  kind  of  material  that 
is  to  be  cultured. 

Urine:  Should  always  be  obtained  by  sterile  catheter,  after  the 
external  meatus  has  been  appropriately  cleansed,  and  drawn  off  into 
a  sterilized  flask  or  bottle,  to  which  no  preservative  should  be  added. 
It  is  better  to  catheterize  the  day  specimen  into  one  receptacle  and 
the  night  urine  into  a  separate  one. 

Feces:  Should  be  obtained,  urine- free,  and  specimens  from  first 
and  last  portion  of  the  stool  obtained  and  studied. 

Sputum:  Should  be  obtained  with  greatest  care,  because  for 
practical  purposes  no  mouth  is  germ-free,  and  alveolar  pyorrhoea, 
infected  tonsils,  and  the  like  are  so  common.  Before  retiring,  the 
mouth  should  be  carefully  rinsed  with  sterile  water  and  the  teeth 
brushed  with  sterile  toothbrush,  and  a  closed  vessel  containing 
sterile  water  placed  at  the  bedside.  In  the  morning  the  mouth 
should  again  be  rinsed  thoroughly  with  the  sterile  water,  gargled, 
and  with  the  brush  re-sterilized,  by  dipping  in  boiling  water,  the 
teeth  should  be  thoroughly  brushed  and  then  a  few  mouthfuls  of 
clean  sterile  water  should  be  swallowed.  After  this  the  sputum 
should  be  expelled  by  coughing  and  caught  in  serial  sterilized  wide- 
mouth  bottles  (with  sterile  corks),  and  it  is  best  that  only  one  or 
two  masses  of  sputum  should  be  expelled  into  any  one  bottle  and 
the  bottles  labelled  and  sent  at  once  to  the  bacteriologist  for  im- 
mediate examination.  The  sputum  should,  after  direct  examination 
of  stained  specimens  to  determine  morphologically  the  different 
types  that  may  be  present,  be  then  "  whipped  "  through  several 
Petri  dishes  containing  sterile  water  to  further  free  the  bacteria 
from  surface  contamination,  and  the  final  washed  specimen  planted 
upon  the  different  culture  media  that  will  appear  best  suited  for 


Am.  Jour.  Pharm. 
May,  1914. 


Autogenous  Vaccines. 


213 


their  recovery  in  pilre  culture,  as  judged  from  the  findings  on  the 
first  direct  examination. 

Cultures  taken  from  boils,  or  from  infected  sinuses,  from  acne 
pustules,  from  tonsillar  follicles,  and  the  like,  should  be  made  only 
after  thorough  appropriate  cleansing  and  disinfection  of  surface 
relations,  and  then  taken  from  a  second  or  third  portion  of  the 
material,  discarding  the  first,  by  means  of  a  platinum  wire  or  a 
sterile  capillary  glass  pipette  inserted  well  within  the  cavity. 

Cultures  from  eye,  ear,  or  nose  should  have  appropriate  measures 
to  secure  success. 

Blood  specimens  should  always  be  obtained  from  a  vein,  pref- 
erably at  the  bend  of  the  elbow,  by  means  of  an  all-glass  sterilized 
syringe  of  a  capacity  not  less 'than  5  c.c.  It  is  rarely  necessary 
to  cut  down  on  a  vein,  but  the  arm  should  be  thoroughly  sterilized 
by  tincture  of  green  soap  and  water,  by  5-10  per  cent,  lysol,  by 
absolute  alcohol,  and  finally  by  ether;  personally  I  prefer  not  to  use 
iodine.  It  is  better  to  moderately  tourniquet  the  upper  arm  before 
sterilizing  the  field  in  order  to  prevent  thin- walled  veins  from  col- 
lapsing under  the  pressure.  The  blood  should  be  immediately  plated 
and  flasked  in  peptone  and  dextrosed  broth. 

In  Pulmonary  Abscesses:  In  suitable  cases  material  may  be 
obtained  by  lung  puncture  in  the  following  way :  After  sterilizing 
the  chest  wall  in  the  same  manner  as  for  blood  cultures,  the  needle 
attached  to  an  all-glass  syringe,  containing  3  c.c.  of  peptone  broth, 
should  be  plunged  into  the  lung  at  the  proper  point,  as  determined 
beforehand  by  clinical  means,  and  1  c.c.  of  the  broth  introduced 
and  then  reaspirated  as  far  as  possible  and  tubed.  This  measure 
will  yield  results  in  many  cases  properly  selected  clinically. 

After  getting  suspected* infected  material,  direct  examination  by 
means  of  variously-stained  slide  specimens  should  be  made  to 
determine  morphologically  and  by  staining  reactions  and  relations 
whether  one  or  more  types  of  organisms  are  present,  and,  if  the 
latter,  how  many  and  what  types,  and  then,  aided  by  this  knowledge, 
proceed  to  utilize  the  various  culture  media  that  will  best  ensure 
recovery  of  each  organism  in  pure  culture.  Here  is  where  the 
thoroughly-trained  bacteriologist  will  succeed  and  in  the  shortest 
time.  It  is  often  exceedingly  difficult  to  recover  a  shyly-growing 
streptococcus  or  tubercle  bacillus  occurring  in  small  numbers,  let  us 
say  from  a  urine  practically  alive  with  the  Bacillus  coli.  This  may 
be  accomplished  by  inhibiting  or  attenuating  the  growth  of  the 


214 


Autogenous  Vaccines. 


{Am.  Jour.  Pharm. 
May,  1914. 


hardier,  more  freely  growing  organism  by  treating  the  culture 
medium  in  an  appropriate  manner,  but  unless  this  is  accomplished 
it  will  be  seen  at  once  how  useless  it  is  to  successfully  treat  a 
pyelitis  of  streptococcal  or  tubercular  origin  by  using  only  the 
B.  coli  in  the  vaccine  preparation.  Hence  the  failure  of  many 
autogenous  vaccines  that  are  bacteriologically  imperfect  or  in- 
complete. 

In  many  cases  of  chronic  gleet,  however,  the  gonococcus  is 
absent  and  the  catarrhal  inflammation  kept  alive  by  secondary  in- 
vaders, which  may  then  in  combination  serve  for  cure  in  absence  of 
the  primary  invader. 

After  getting  out  every  bacterial  group  contained  in  a  given 
specimen,  each  in  pure  culture,  these  should  then  be  studied  with  a 
view  to  their  share  in  the  production  or  continuation  of  the  disease 
in  question,  and,  guided  by  experience,  clinical  as  well  as  bacterio- 
logical, a  final  judgment  of  the  organisms  concerned  may  be  passed 
and  the  proper  ones  selected  for  use  in  the  vaccine.  They  may 
all  be  combined  in  a  single  ampoule  or  may  be  placed  singly  or  in 
pairs.  Only  the  lower  dosages,  however,  can  be  reached  by  making 
a  mixed  vaccine  composed  of  many  elements,  on  account  of  the 
combined  dosage  being  too  high  to  permit  of  safe  injection. 

We  can  now  proceed  to  prepare  the  vaccine,  in  which  the 
following  steps  are  concerned: 

1.  To  obtain  an  emulsion  containing  the  bacteria  in  purity — an 
emulsion  with  a  uniform  suspension  and  as  free  from  bacterial 
clumping  as  possible. 

2.  To  standardize  the  emulsion — that  is,  to  determine  how 
many  bacteria  are  contained  in  each  cubic  centimetre. 

3.  To  kill  the  bacteria  in  the  emulsion  and  then  tube  them — or 

4.  To  decide  upon  the  dosage  of  each  ampoule  or  set  of  am- 
poules ;  to  tube  them  still  alive  and  then  kill  them. 

5.  To  label,  effectively,  each  ampoule  and  place  them  in  sets 
of  ten  in  compartment  boxes  or  cartons,  the  lids  of  which  are  to  be 
specifically  marked  with  the  names  of  the  organisms  they  contain 
and  in  what  dosage,  and  most  particularly  with  directions  for  their 
use. 

6.  To  be  sure  that  all  "  controls  "  are  sterile  before  allowing 
the  vaccine  set  to  leave  the  laboratory  for  use. 

I  shall  not  in  this  paper  enter  in  detail  into  the  technic  required 
in  the  actual  preparation  of  the  vaccine,  but  I  want  to  say  a  word 


Am.  Jour.  Pharm. 
May,  1914. 


Autogenous  Vaccines. 


215 


or  two  of  caution  to  most  carefully  consider  the  best  ways  of  killing 
the  bacteria  without  impairing  .their  immunizing  properties.  This 
can  only  be  accomplished  by  a  thorough  knowledge  of  and  observ- 
ance of  the  thermal  and  chemical  death-point  of  each  group  of  organ- 
isms :  a  knowledge  that  will  tell  you  which  bacteria  should  be 
killed  by  heat  and  which  by  chemical  measures,  or  by  a  combination 
of  the  two.  If  by  heat,  at  what  temperature  and  for  how  long 
sustained  ?  If  by  chemical  sterilization,  by  what  chemical  and  in  what 
strength?  I  have  known  many  an  autogenous  vaccine — otherwise 
quite  appropriately  selected  bacteriologically  and  otherwise  fault- 
lessly prepared — to  be  inert  and  to  fail  absolutely  therapeutically 
for  no  other  reason  than  that  the  thermal  and  chemical  death-points 
were  not  carefully  ascertained.  And  I  doubt  not  that  this  applies 
equally  to  many  stock  vaccines. 

Have  we  in  vaccine  therapy  a  means  sufficient  to  combat  all 
types  of  bacterial  infections?  I  would  answer  emphatically  "no," 
and  I  would  add  that  harm  may  often  come  from  their  indiscriminate 
use  and  in  the  hands  of  the  inexperienced  and  careless. 

In  epidemic  meningitis,  in  typhoid  fever,  in  pneumonia,  in  gen- 
eralized bacteremia,  with  or  without  ulcerative  endocardial  lesions, 
the  use  of  vaccines  for  curative  purposes  has  not  been  attended 
with  great  success,  although  occasionally  a  case  is  seen  in  which 
amelioration  in  severity  of  symptoms  has  taken  place  which  rightly 
or  wrongly  has  been  ascribed  to  the  use  of  the  vaccine.  I  am  by  no 
means  yet  convinced  that  their  use  in  such  cases  is  unjustifiable, 
and  believe  that  we  may  yet  arrive  by  experience  at  some  method 
of  establishing  proper  dosages  and  proper  intervals  of  injection 
for  this  class  of  acute  fulminating  infections  that  will  produce 
better  results. 

The  most  suitable  field  for  vaccines  and  the  field  in  which  the 
most  brilliant  results  have  been  obtained  lies  in  treatment  of 
diseases,  acute  or  chronic,  that  have  a  local  focus  of  infection,  such 
as  furunculosis,  carbuncles,  abscesses,  various  bone  infections,  such 
as  osteomyelitis,  various  skin  infections,  such  as  acne  vulgaris, 
infected  sinuses,  pyelitis,  empyema,  various  infections  of  the  mouth, 
such  as  pyorrhoea  alveolaris,  infections  of  the  nose  and  nasal  pas- 
sages and  various  post-gonorrhceal  conditions,  and  various  con- 
ditions of  the  respiratory  tract. 

And  now  a  final  word  as  to  why  vaccines  fail  in  the  hands  of 
many  workers,  even  in  the  above  field  of  election — chiefly  because 


216  Chemistry  of  a  Cup  of  Coffee.  |A%^9Pi4arm' 

of  insufficient  knowledge  governing  the  general  laws  of  dosage  and 
time  intervals  of  injection;  by  selecting  inappropriate  points  of 
injection;  by  disregarding  the  best  time  of  day  at  which  injection 
should  be  given,  so  that  the  patient  isn't  safeguarded  during  the 
"  negative  phase  "  period  at  which  his  antibody  formation  is  at  the 
lowest  ebb,  etc.  For  many  of  these  points  I  would  refer  the  student 
or  interested  worker  to  a  close  perusal  of  monographs  on  this  sub- 
ject, notably  Allen  on  "  Vaccine  Therapy." 

Finally,  I  would  call  attention  to  a  common  cause  of  failure  in 
a  neglect  to  realize  that  autogenous  vaccines  need  to  be  frequently 
freshly  renewed — i.e.,  a  new  culture  taken  and  a  new  vaccine  pre- 
pared from  cultures  that  represent  more  nearly  the  status  prcusens 
of  the  case;  for  it  frequently  happens  that  in  long  chronic  con- 
ditions the  bacteria,  by  mutation  or  other  biological  properties,  be- 
come adapted  more  or  less  to  the  antibodies  formed  in  the  tissues 
of  the  host. 

I  was  asked,  before  reading  this  paper  before  this  body,  whether 
I  did  not  think  it  quite  feasible  and  quite  proper  for  druggists  to 
establish  autogenous  and  stock  vaccine  departments  for  the  purpose 
of  themselves  making  these  products.  I  think  I  must  already  have 
answered  this  question  to  most  of  you.  I  do  not  think  it  is  practical 
nor  fitting  that  you  should,  nor  do  I  believe  that  it  would  prove 
commercially  a  success.  And  let  me  close  with  the  words  of  Sir 
Almroth  Wright,  one  of  the  pioneers  in  this  work,  who  states  that 
for  such  skilled  service  as  that  demanded  for  vaccine  therapy  "  is 
required  a  man  who  has  spent  years  of  study  to  master  the  technic ; 
to  know  how  to  make  the  vaccines,  to  know  where  to  look  for 
the  microbes,  to  know  how  to  isolate  them,  and,  most  of  all,  a  man 
with  sufficient  experience  and  ability  to  apply  all  these  things." 

1901  Pine  Street,  Philadelphia,  Pa. 


THE  CHEMISTRY  OF  A  CUP  OF  COFFEE. 

From  time  to  time  numerous  analyses  of  coffee  have  been  made 
and  published  which,  while  giving  some  insight  into-  the  chemistry 
of  the  coffee  berry,  have  not  necessarily  enlightened  us  as  to  the 
position  of  affairs  in  regard  to  the  liquor  obtained  when  coffee  is 
prepared  in  the  way  commonly  enjoined.  The  chemistry  of  the  cup 
of  coffee  will  obviously  leave  out  of  consideration  the  chemistry  of 


Am.  Jour.  Pharna.  1 
May,  1914.  / 


Chemistry  of  a  Cup  of  Coffee. 


217 


the  "  grounds."  It  is  the  infusion  with  which  the  following  labora- 
tory notes  deal,  and  certain  fresh  indications,  we  believe,  have  been 
obtained  which  are  worth  presenting  in  view  of  their  medical  in- 
terest. The  story  is  far  from  complete,  but  there  are  interesting 
incidents  in  it  which,  as  far  as  it  goes,  are  worth  recording. 


A  Comparison  between  Coffee  and  Tea. 

From  a  pharmacological  or,  what  should  amount  to  the  same,  a 
dietetic  standpoint  tea  or  coffee  ought  in  certain  ways,  at  all  events, 
to  act  similarly,  since  both  contain  the  alkaloid  caffeine  which  has  a 
well-known  and  marked  effect  of  stimulation  upon  the  central 
nervous  system.  It  is  generally  admitted,  however,  that  the  two 
beverages,  though  having  one  thing  in  common,  afford  different 
results.  Tea,  it  is  well  to  point  out,  contains  a  much  larger  propor- 
tion of  the  alkaloid  than  coffee,  but  in  the  preparation  of  tea  in 
ordinary  domestic  practice  a  much  smaller  quantity  of  material  is 
used  than  is  the  case  with  coffee.  A  common  formula  enjoined  in 
the  making  of  tea  amounts  to  the  preparation  of  1.25  per  cent,  in- 
fusion of  the  leaf.  Similarly,  in  the  preparation  of  coffee  the  quan- 
tity of  coffee  usually  directed  to  be  used  signifies  a  6  per  cent,  decoc- 
tion. Since  tea  contains  from  3  to  4  per  cent,  of  caffeine,  and 
coffee  seldom  more  than  1  per  cent.,  it  follows  that  as  regards  this 
alkaloid  both  infusions  of  coffee  and  tea  made  on  common  domestic 
lines  will  contain  practically  the  same  amount  of  caffeine  volume  for 
volume  of  fluid.  The  inference  is  that  whether  it  be  a  cup  of  coffee 
or  of  tea,  the  dose  of  alkaloid  will  be  the  same.  But  according  to 
the  present  investigation  the  caffeine  in  coffee  infusion  has  quite 
different  associates  from  those  in  tea.  This  would  appear  to  be  the 
case,  inasmuch  as  while  little  caffeine  is  extracted  from  tea  by  cold 
water,  we  find  that  practically  the  whole  of  the  caffeine  in  coffee  is 
taken  out.  There  seems  to  be  little  doubt,  as  we  have  shown  in  pre- 
vious articles  upon  tea,1  that  the  caffeine  in  tea  is  for  the  most  part 
combined  with  tannin  in  the  form  of  caffeine  tannate,  which  is  not 
very  soluble  in  cold  water,  but  is  easily  soluble  in  hot  water.  We 
think  this  is  an  important  observation,  for  it  points  to  the  proba- 
bility of  caffeine  existing  in  coffee  in  a  quite  different  form  which  is 

1 "  The  Chemistry,  Physiology,  and  ^Esthetics  of  a  Cup  of  Tea,"  The 
Lancet,  Jan.  7th,  191 1,  and  Dec.  2nd,  191 1. 


218  Chemistry  of  a  Cup  of  Coffee.  {A%JaXi9Pilarm' 

easily  soluble  in  cold  water.  Subsequent  experiments  showed  that 
the  caffeine  in  coffee  is  combined  with  a  peculiar  acid  allied  possibly 
to  tannic  acid,  but  exhibiting  different  properties  from  the  tannin 
present  in  tea.  Thus  this  acid  (it  has  been  called  caffetannic  acid  by 
some  observers)  is  not  particularly  astringent,  has  a  sour  coffee-like 
taste,  does  not  coagulate  gelatin,  gives  a  light  green  colouration  with 
perchloride  of  iron  (whereas  tannic  acid  of  tea  turns  it  black),  does 
not  make  caffeine  solutions  thick  as  does  tannic  acid,  does  not  pre- 
cipitate alkaloids — e.g.,  quinine — and,  in  fact,  shows  altogether  dif- 
ferent properties  from  the  tannic  acid  of  tea.  It  gives  a  precipitate, 
however,  with  lead  acetate  from  which  the  acid  can  be  separated  by 
sulphuretted  hydrogen.  When  coffee  infusion  is  saturated  with 
ammonium  sulphate  a  precipitate  is  obtained  which  contains  a  small 
proportion  of  the  total  caffeine  in  the  free  state,  whereas  a  tea  infu- 
sion similarly  treated  gives  an  abundant  precipitate  containing  nearly 
all  of  the  caffeine,  this  precipitate  according  to  our  observations  con- 
sisting chiefly  of  caffeine  tannate. 

The  Absorption  of  Caffeine  Modified  by  its  Associates. 

The  caffeine  tannate  of  tea  is  precipitated  by  weak  acids,  and  the  * 
presumption  is  that  it  is  precipitated  by  the  gastric  juice,  and  there- 
fore the  caffeine  is  probably  not  absorbed  until  it  reaches  the  alkaline 
alimentary  tract.  In  the  case  of  coffee,  however,  in  whatever  form 
the  caffeine  may  be  present,  it  is  soluble  in  both  alkaline  and  acid 
fluids,  and  therefore  the  absorption  of  the  alkaloid  probably  takes 
place  in  the  stomach.  This  fact  may  have  an  important  physiological 
significance  when  we  consider  the  comparative  stimulating  effects  of 
the  two  beverages.  If  our  view  is  correct  coffee  should  act  more 
promptly  than  tea  as  a  stimulant  and  restorative,  looking  to  its 
physiological  action  as  due  for  the  most  part  to  caffeine.  In  prac- 
tice it  is  generally  accepted  that  coffee  is  a  more  powerful  restorative 
than  tea.  The  use  of  strong  coffee  as  an  antidote  in  poisoning  by 
narcotics,  notably  morphia,  is  of  interest  in  this  connexion.  Tea  is 
mentioned  for  the  same  purpose,  but  only  rarely.  Apart  from 
the  consideration  that  caffeine  has  probably  a  more  rapid  action 
when  taken  in  the  form  of  coffee  than  in  the  form  of  tea,  because 
the  caffeine  in  coffee  is  more  readily  absorbed,  it  must  also  be  re- 
membered that  coffee  is  often  made  with  a  generous  proportion  of 
the  powdered  bean,  as  in  the  case  of  the  after-dinner  "  black  "  coffee, 


'm'MJa°yUri9i4arm"}        Chemistry  of  a  Cup  of  Coffee.  219 

the  view  being  that  the  secret  of  good  coffee  is  to  make  it  strong. 
This,  of  course,  is  an  entirely  aesthetic  demand,  which  may  likely 
enough  be  opposed  to  physiological  morality. 


The  Strength  of  Cold  Water  Extracts  of  Coffee  Compared 
with  Boiling  Water  Extracts. 

The  fact  that  the  caffeine  in  coffee  is  completely  soluble  in  cold 
water  suggested  making  a  comparison  as  to  the  composition  of  the 
cold  and  hot  water  infusions  in  regard  to  other  constituents.  For 
this  purpose  several  types  of  coffee  were  chosen,  all  of  which  reached 
this  country  through  Costa  Rica.  As  will  be  seen  from  the  accom- 
panying table,  the  varieties  examined  were  as  follows :  Raw  {i.e., 
unroasted)  Costa  Rica,  common  quality;  raw  Costa  Rica,  finest 
quality ;  pale  roasted  Costa  Rica,  common  quality ;  pale  roasted  Costa 
Rica,  finest  quality ;  high  roasted  Costa  Rica,  common  quality ;  and 
high  roasted  Costa  Rica,  finest  quality.  The  results  are  instructive, 
and  we  may  proceed  to  consider  the  differences  in  composition  of 
the  infusions,  both  cold  and  hot,  shown  where  raw,  pale  roasted, 
and  high  roasted  coffee  are  employed,  and  the  relationships,  if  any, 
of  these  differences  to  the  discrimination  supplied  by  the  expert 
taster,  who  describes  a  particular  coffee  as,  in  his  own  words,  "  com- 
mon "  or  "  finest." 

It  is  a  somewhat  remarkable  fact  that  cold  water  extracts  from 
coffee  the  same  weight  of  materials  as  boiling  water,  but  it  must 
be  admitted  that  the  former  infusion  is  somewhat  less  palatable 
than  the  latter.  Chemically,  however,  there  is  little  difference  be- 
tween them,  and  we  may  presume  that  physiologically  a  cold  water 
extract  of  coffee  will  be  much  the  same  as  a  hot  water  infusion,  leav- 
ing out  aesthetic  considerations,  although  these,  of  course,  are  exceed- 
ingly important,  from  all  dietetic  aspects.  It  is  probable  that  cold 
water  fails  to  extract  certain  oily  bodies  or  fats  which  contribute 
attractive  taste  and  aroma.  The  total  extract  is  frequently  higher 
in  cold  than  in  hot  water.  And  not  only  is  caffeine  extracted  from 
coffee  equally  well  by  cold  and  hot  water,  but  this  is  true  of  the 
mineral  salts  and  of  the  peculiar  acid  known  as  caffetannic  acid,  the 
acid  which  corresponds  to  the  tannin  of  tea.  In  regard  to  the  pro- 
portion of  materials  soluble  in  cold  water  coffee  shows  an  entirely 
different  result  to  tea,  inasmuch  as  while  coffee  yields  about  25  per 
cent,  of  its  weight  to  cold  water  (an  amount  which  is  not  increased 


220 


Chemistry  of  a  Cup  of  Coffee.  { 


Am.  Jour.  Pharm. 
May,  1914. 


when  hot  water  is  used)  tea  yields  only  12  per  cent,  of  its  weight  to 
cold  water,  which  is  increased  to  25  per  cent,  when  the  infusion  is 
made  with  hot  water.  Again,  cold  water  extracts  from  tea  only  17.5 
per  cent,  of  its  total  caffeine,  while  from  coffee  it  extracts  the  whole. 
Similarly,  cold  water  extracts  from  tea  13  per  cent,  of  its  total  tan- 
nin, while  coffee  under  the  same  treatment  yields  practically  the 
whole  of  its  caffetannic  acid. 

The  Effect  of  Roasting. 

An  infusion  of  green  or  unroasted  coffee  is  singularly  nasty  to 
the  palate,  and  it  follows  that  the  roasting  process  renders  coffee 
the  palatable  article  that  it  is.  The  chemistry  of  roasting  amounts 
largely  to  a  caramelisation  process,  during  which  certain  oils  and 
aromatic  principles  are  formed  as  products  of  a  mild  destructive  dis- 
tillation. Curiously  enough,  there  is  little  loss  of  caffeine  in  this 
process,  as  our  results  show,  which  is  remarkable  in  view  of  the 
fact  that  caffeine  sublimes  at  high  temperatures.  There  are  two 
degrees  of  roasting  adopted — viz.,  pale  roasting  and  high  roasting. 
The  important  chemical  effect  of  roasting,  according  to  our  analyses, 
is  to  diminish  considerably  the  amount  of  caffetannic  acid.  If  the 
figures  in  the  table  be  consulted  it  will  be  seen  that  while  in  an 


The  Analysis  of  Hot  and  Cold  Infusions  of  Coffee. 


Constituent. 

Raw  Costa  Rica 
(common). 

Raw  Costa  Rica 
(finest). 

Pale  roasted  Costa 
Rica  (common). 

Hot 
infusion. 

Cold 
infusion. 

Hot 
infusion. 

Cold 
infusion. 

Hot 
infusion. 

Cold 
infusion. 

Total  extract  

Ash  of  extract  

Caffetannic  acid  

29.16 
4.16 
9.60 
1. 00 

30.83 
3-88 
8.63 
1-33 

29.60 
4.00 
9.66 
1. 21 

3i.5o 
3-88 
7.83 
1.56 

25-33 
4.16 
6.10 
1. 11 

24.00 
5-66 
5.8o 
1. 11 

Constituent. 

Pale  roasted  Costa 
Rica  (finest). 

High  roasted  Costa 
Rica  (common). 

High  roasted  Costa 
Rica  (finest). 

Hot 
infusion 

Cold 
infusion. 

Hot 
infusion. 

m  Cold 
infusion. 

Hot 
infusion 

Cold 
infusion. 

23.SO 

25.66 

24.30 

24.00 

25.60 

23.00 

3-50 

4-50 

4.66 

4.00 

4.00 

4-50 

Caffetannic  acid  

6.60 

5-90 

3-90 

3.16 

363 

3.87 

Total  caffeine  

1. os 

1.06 

1.23 

1. 11 

1.05 

1.20 

Am.  Jour.  Pharm. 
May,  1914. 


Chemistry  of  a  Cup  of  Coffee. 


221 


infusion  of  raw  coffee  (unroasted)  the  caffetannic  acid  amounts  to 
9.60  per  cent.,  it  is  in  the  pale  roasted  6.60  per  cent.,  while  by 
further  roasting,  as  in  the  "  high  roasted,"  it  is  reduced  in  the 
infusion  from  3.63  to  3.90  per  cent.  What  part  cafTetannic  acid  ex- 
actly plays  as  a  dietetic  constituent  of  coffee  it  is  difficult  to  say, 
but  if  it  should  prove  to  be  an  undesirable  element,  then  the  high 
roasted  coffees  are  least  open  to  objection  on  this  account.  It  may 
be  noticed  also  that  the  raw  coffee  yields  a  greater  percentage  of 
soluble  constituents  to  both  cold  and  hot  water  than  high  roasted 
coffee,  the  pale  roasted  coffee  showing  intermediate  results.  Roast- 
ing, amongst  other  things,  has,  therefore,  the  effect  probably  of 
rendering  certain  bodies  insoluble — e.g.,  albumins — while  the  slight 
burning  effect  upon  carbohydrates  would  produce  possibly  some  free 
and  of  course  insoluble  carbon. 

Quality  of  Coffee  in  Relation  to  Chemical  Composition. 

From  the  results  recorded  in  the  table  it  will  be  seen  that  no 
definite  relation  cambe  traced  between  the  aesthetic  quality  of  coffees, 
classed  respectively  as  "  common  "  and  "  finest,"  and  the  chemical 
composition  of  the  infusions  which  they  yield.  It  may  be  noted  that 
there  is  no  important  difference  in  the  amount  of  the  drug  caffeine 
when  the  common  and  finest  varieties  are  examined.  It  is  probable 
that  the  aesthetic  values — flavour,  body,  aroma,  and  so  forth — are  re- 
lated in  some  way  to  the  amounts  of  oil  bases  or  aromatic  principles 
present,  and  these  are  in  any  case  minute.  Whether  they  are  present 
in  appreciable  quantity  or  not  doubtless  depends  upon  the  care  spent 
upon  the  roasting  process.  At  any  rate,  it  is  conceivable  that  a  point 
in  the  roasting  process  could  be  reached  which  would  deprive  the 
coffee  of  all  attractive  flavour,  while  it  is  certain  that  the  infusion  of 
the  raw  unroasted  berry  is  not  fit  to  drink  on  account  of  its  un- 
pleasant taste.  Recently  it  has  been  announced  on  more  than  one 
occasion  that  pyridin  is  an  important  constituent  of  coffee.  We  have 
certainly  found  it  present,  but  not  in  sufficient  quantities  to  estimate. 
It  is  rather  a  curious  fact  that  some  authorities  mention  that  coffee 
often  relieves  asthma,  while  pyridin  is  described  as  "  useful  in  the 
treatment  of  asthma  "  and  "  beneficial  in  cardiac  dyspnoea,  emphy- 
sema, and  angina  pectoris,"  and,  finally,  that  "  it  is  probably  the 
relieving  agent  of  various  cigarettes  and  powders  smoked  or  burnt 
for  asthma  and  whooping-cough."    Another  constituent  of  coffee 


222 


Chemistry  of  a  Cup  of  Coffee. 


Am.  Jour.  Pharm. 
May,  1914. 


produced  by  roasting  is  caffeol,  a  nitrogen-containing  oil,  but  it 
would  be  impossible  to  differentiate  the  quality  of  coffee  upon  an 
analysis  pursued  in  this  direction,  inasmuch  as  the  amount  found 
does  not  exceed  more  than  0.06  per  cent.  It  is  doubtful  whether  it 
has  any  further  value  from  a  dietetic  point  of  view  than  that  sup- 
plied by  its  influence  in  pleasing  the  senses.  When  isolating  caffeine 
from  coffee  infusion  the  solvent  (chloroform)  takes  out  also  a  non- 
crystalline substance  which  unlike  caffeine  is  soluble  in  ether.  This 
substance  has  a  very  strong,  pleasant,  but  somewhat  bitter  flavour 
of  coffee.  The  yield  is  different  according  to  the  quality  of  the 
coffee  examined,  and  it  is  possible  that  this  principle  is  a  determining 
factor  in  the  judgment  given  by  the  expert  coffee  taster.  It  is  a 
product  of  roasting  and  does  not  exist  in  raw  coffee. 

Food  Value  of  Coffee. 

The  infusion  of  coffee  presents  practically  very  little  material 
that  is  of  direct  nourishing  value,  but  by  diminishing  nervous 
fatigue,  by  virtue  chiefly  of  the  caffeine  present,  it  may  increase 
muscular  power.  It  is  not  itself  a  builder  of  tissue.  The  use  of  coffee 
after  dinner,  it  is  of  interest  to  note,  is  justified  in  a  large  number 
of  cases  by  the  fact  of  its  stimulating  effect  upon  the  vital  centres, 
and  it  is  said  to  serve  to  some  extent  as  an  antidote  to  alcohol.  It 
is  commonly  claimed  to  remove  drowsiness ;  as  a  matter  of  fact, 
in  many  subjects  it  produces  drowsiness,  but  this  is  usually  followed 
quickly  by  marked  wakefulness.  The  practice  of  drinking  coffee 
after  a  meal  for  the  sake  of  the  stimulus  which  is  experienced  has 
much  to  be  said  in  its  favour  dietetically.  There  is  no  reason  for  sup- 
posing that  coffee  possesses  any  value  as  a  food.  The  berry  con- 
tains a  quite  important  proportion  of  fatty  substances  (12  per  cent, 
average),  but  these  are  necessarily  excluded  from  the  infusion,  as 
owing  to  their  insolubility  they  remain  in  the  "  grounds." 

According  to  our  analyses  again  the  protein  contents  of  a  cup 
of  coffee  are  small,  approximating  to  1.25  per  cent,  of  the  coffee 
extracted.  This  amount  can  have  little  dietetic  significance.  There 
is  also  a  trifling  quantity  of  dextrin  and  sugar  present  besides  traces 
of  alcohol,  which  again  can  possess  no  importance  from  a  physio- 
logical point  of  view. — The  Lancet,  Nov.  29,  1913,  pp.  1 563-1 565. 


Am.  Jour.  Pharm. 
May,  1914. 


Book  Reviews. 


223 


BOOK  REVIEWS. 

Pharmaceutical  Botany.  By  Heber  W.  Youngken,  Assistant 
Professor  of  Botany  and  Pharmacognosy  at  the  Medico-Chirnrgical 
College,  Philadelphia.    P.  Blakiston's  Son  &  Co.,  Philadelphia. 

To  speak  of  this  little  book  of  less  than  a  hundred  pages  as  a 
dictionary  or  a  glossary  is  not  to  belittle  its  value  to  the  student.  The 
illustrations,  as,  for  example,  those  on  stem  and  leaf  structure,  are 
especially  well  chosen,  and  their  pictorial  value  is  worth  many  words 
of  text,  which,  of  course,  is  not  a  factor  of  this  book.  From  almost 
any  aspect  of  thought  the  book  seems  like  a  list  of  terms,  but  these 
terms  are  well  arranged  and  with  a  good  regard  to  system.  The 
desire  to  make  the  definitions  brief  has  made  them  in  many  cases 
almost  meaningless  except  just  as  a  reminder  to  one  who  already 
knows  what  the  term  means. 

As  a  whole,  the  acknowledged  desire  of  the  author  has  been  well 
attained,  but  there  is  a  question  whether  such  an  object  is  especially 
advisable.  A  student  is  apt  to*  be  just  as  human  as  the  average  per- 
son with  a  consequent  eagerness  to  have  before  him  a  volume  which 
is  "  readable  "  even  though  it  is  for  purposes  of  study.  The  feeling 
arises  in  us,  as  we  look  over  the  volume  in  hand,  that  it  is  a  mighty 
nice  little  book  to  turn  to  once  in  a  while,  but  that  it  would  rather 
strain  our  devotion  to  science  if  we  were  called  upon  to  use  it  as  a 
text-book  from  which  to  gain  our  first  insight  into  a  new  subject. 

A.  K.  Lobeck. 

Annual  Reprint  of  the  Reports  of  the  Council  on  Phar- 
macy and  Chemistry  of  the  American  Medical  Association 
for  1913,  with  the  Comments  that  have  appeared  in  the  Journal. 

"  The  more  strictly  scientific  parts  of  the  reports,  both  from  lack 
of  space  and  because  of  their  technical  nature,  have  been  abstracted 
or  entirely  omitted  from  the  reports  as  published  in  the  Journal. 
Believing  that  these  scientific  investigations  should  be  available  to 
scientists  in  general,  especially  to  chemists,  pharmacologists,  and 
others  interested  in  medicine,  the  Council  has  authorized  the  prep- 
aration of  this  volume,  containing  the  complete  reports  of  the  Coun- 
cil adopted  prior  to  January  1,  19 14,  as  well  as  the  comments  which 
have  appeared  at  the  time  of  publication." 

These  reports  are  a  valuable  addition  to  the  literature  that  has 


224 


Current  Literature. 


Am.  Jour.  Pharm. 
May,  1914. 


accumulated  in  the  last  few  years  on  proprietary  remedies  and 
nostrums. 

Previous  to  the  last  decade  investigative  work  of  this  sort  in 
reference  to  remedies  of  this  kind  was  hardly  thought  of,  although 
there  may  have  been  dreamers  who  had  hopes  and  visions  of  what 
the  future  might  bring  forth.  We  do  not  use  the  word  "  dreamers  " 
in  any  offensive  sense.  Dreamers  with  initiative  and  honesty  of 
purpose  are  the  compelling  force  in  this  world,  and  it  is  gratifying 
to  know  that  there  are  men  of  this  type  in  medicine  and  pharmacy 
who  are  willing  to  work  disinterestedly  for  the  body  politic. 

Pharmacists  who  desire  to  add  to  their  efficiency  and  usefulness 
would  do  well  to  add  these  reports,  which  have  been  appearing  for 
several  years,  to  their  libary. 

John  K.  Thum. 

New  and  Nonofficial  Remedies,  1914:  Containing  Descrip- 
tions of  the  articles  which  have  been  Accepted  by  the  Council  on 
Pharmacy  and  Chemistry  of  the  American  Medical  Association 
Prior  to  January  1,  1914. 

This  work  epitomizes  one  phase  of  the  revolution  that  has  taken 
place  in  medicine  the  last  decade.  It  typifies  the  passing  from  dark- 
ness into  the  light  of  reason  of  things  pharmacological,  or  rather  the 
exploitation  of  modern  materia  medica.  Indeed,  it  fills  a  long-felt 
want  in  both  the  profession  of  medicine  and  pharmacy.  When  one 
stops  to  consider  the  inaccessibility  of  information  relating  to  un- 
official remedies  previous  to  its  publication  it  hardly  seems  possible 
that  we  ever  got  along  without  it. 

Essential  information  relating  to  biological  remedies  such  as 
serums,  vaccines,  and  tuberculin  preparations  is  given  in  a  manner 
convenient  to  the  seeker  after  such  knowledge. 

John  K.  Thum. 


CURRENT  LITERATURE. 

Uniformity  in  Drug  Standards. — In  a  contribution  to  the 
Journal  of  the  Kansas  State  Medical  Society,  entitled  "A  Plea  for 
Uniformity  in  Drug  Standards  and  for  Uniform  Requirements  in 
Dispensing,"  L.  E.  Sayre  makes  some  interesting  observations. 
"If  what  is  prohibited  within  a  state  is  permitted  beyond  its  borders, 


Am.  Jour.  Pharm. 
May,  1914. 


Current  Literature. 


225 


tfre  statutes  of  prohibition  become  not  only  inefficient,  but  most  use- 
less. If  what  is  prohibited  within  a  drug  store  is  permitted  in  a 
physician's  dispensary,  the  law  likewise  becomes  measurably  inop- 
erative as  far  as  the  public  is  concerned." 

He  makes  the  statement  that  such  conditions  exist  and  that  in 
some  of  the  different  states  the  evil  has  been  exposed.  He  quotes 
Mr.  Roemer,  who,  at  a  meeting  of  the  New  York  Pharmaceutical 
Association,  made  the  announcement  that  an  investigation  of  some 
of  the  medicines  dispensed  by  physicians  showed  a  sad  state  of 
affairs ;  heroin  tablets  containing  no  heroin,  morphine  tablets  with- 
out morphine,  and  elixir  of  terpin  hydrate  in  which  the  terpin  hydrate 
was  conspicuous  by  its  absence ! 

Mr.  Sayre  believes  that  the  interest  of  the  public  could  be  safe- 
guarded by  the  state  laws  requiring  all  medicine  dispensed  by  phy- 
sicians to  bona  fide  patients  to  conform  to  legal  standards,  and,  fur- 
ther, that  any  place  where  drugs  are  compounded,  dispensed,  or  sold 
should  be  amenable  to  official  inspection. 

If  dispensing  by  medical  men  has  resulted  in  conditions  which 
are  prejudicial  to  the  public  health — and  from  this  standpoint  alone 
should  the  question  be  viewed — then  legislative  regulation  must, 
and  no  doubt  will,  be  undertaken  by  the  various  states.  This  ques- 
tion is  beginning  to  loom  up  as  never  before  and  must  be  settled 
sooner  or  later.  It  probably  would  be  a  good  plan  if  the  various 
state  medical  and  pharmaceutical  societies  at  their  coming  meetings 
for  the  year  were  to  take  hold  and  thresh  this  matter  thoroughly  and 
formulate  some  definite  opinion  upon  the  whole  subject. 

John  K.  Thum. 

Chemical  Examination  of  Dicoma  Anomala.  By  Frank 
Tutin  and  William  J.  S.  Naunton.  The  Wellcome  Chemical  Re- 
search Laboratories,  London. 

The  material  employed  for  this  investigation  consisted  of  the 
entire  air-dried  plant  of  Dicoma  anomala,  Sond.,  obtained  from 
South  Africa. 

An  alcoholic  extract  of  the  plant,  distilled  in  a  current  of  steam, 
yielded  a  small  amount  of  an  essential  oil.  The  portion  of  the  ex- 
tract which'was  soluble  in  water  yielded  a  small  amount  of  a  colorless 
crystalline  glucoside,  and  a  large  amount  of  a  yellow  amorphous 
product,  which,  on  hydrolysis  with  alkali,  gave  3 : 4-  dihydroxycin- 


226  Philadelphia  College  of  Pharmacy.  {Am^\^mi 

namic  acid.  The  aqueous  liquid  contained,  furthermore,  a  quantity 
of  sugar  which  yielded  d-phenylglucosazone,  melting  at  21 8°. 

The  portion  of  the  extract,  which  was  insoluble  in  water,  formed 
a  dark-colored,  resinous  mass.  It  consisted  largely  of  amorphous 
products,  some  of  which  gave  3 : 4-dihydroxycinnamic  acid  on  hy- 
drolysis, and  a  small  amount  of  an  amorphous  alkaloid  was  also 
present.  The  following  definite  substances  were  obtained  from  the 
resin :  Hentriacontane  C31H64 ;  a  phytosterol  C28H460 ;  palmitic, 
stearic,  arachidic,  cerotic,  and  melissic  acids,  together  with  some 
unsaturated  acids  which  appeared  to  consist  chiefly  of  a  compound, 
C16H30O2,  such  as  has  been  obtained  by  Bull  (Ber.,  1906,  39,  3537) 
from  cod-liver  oil. 

________  .   J.  K.  T. 

PHILADELPHIA  COLLEGE  OF  PHARMACY. 
Annual  Meeting. 

The  annual  meeting  of  the  Philadelphia  College  of  Pharmacy 
was  held  March  30th,  at  4  p.m.,  in  the  Library;  the  President, 
Howard  B.  French,  presiding.  Twenty-two  members  were  present. 
The  minutes  of  the  quarterly  meeting  held  December  29th,  191 3, 
were  read  and  approved.  The  minutes  of  the  Board  of  Trustees  for 
December  2nd,  1913,  January  6th,  February  3rd  and  9th  were  read 
by  the  Registrar,  J.  S.  Beetem,  and  approved. 

President  French  delivered  his  Annual  Address,  when  Mr.  Ber- 
inger  moved  that  the  address  be  referred  to  the  Publication  Com- 
mittee, as  there  were  many  items  of  information  that  should  be 
given  to  the  public  through  The  American  Journal  of  Pharmacy, 
particularly  the  items  referring  to  the  instruction  as  given  in  the 
College.  Seconded,  and  so  ordered.  (See  p.  233  in  this  issue  of  this 
Journal.) 

Report  of  the  Publication  Committee  was  read  by  Professor 
S.  P.  Sadtler.  The  Journal  has  been  published  regularly  during 
the  past  twelve  months.  The  financial  statement  presented  shows 
a  creditable  balance  after  paying  all  bills.  It  is  impossible  to  supply 
a  complete  set,  as  some  of  the  earlier  volumes  have  one  or  more 
numbers  missing.  It  is  hoped  that  the  sale  of  back  numbers  will 
increase  so  that  a  general  index  since  1890  can  be  published.  There 
is  need  for  such  an  index,  as  is  shown  by  a  number  of  inquiries  for 


AmM™r\guana-}    Philadelphia  College  of  Pharmacy.  227 

one,  and  even  orders  have  been  received.  In  discussing  the  report 
Mr.  Beringer  asked  if  it  was  possible  to  reprint  the  missing  back 
numbers  in  order  to  supply  complete  sets.  Professor  Remington 
suggested  making  use  of  a  photographic  process,  in  place  of  printing, 
to  replace  back  numbers,  when  Mr.  England  moved  that  in  order  to 
secure  reprints  of  back  numbers  .the  subject  be  referred  to  the 
Publication  Committee,  with  power  to  act.    So  ordered. 

Report  of  Committee  on  Pharmaceutical  Meetings. — Pro- 
fessor Kraemer  said  that  the  work  done  during  the  past  few  years 
has  not  been  all  it  should  be,  owing  to  the  fact  that  (as  there  are 
so  many  pharmaceutical  societies  in  Philadelphia)  there  was  a  cor- 
responding division  of  energy.  Yet  there  are  some  indications  that 
our  College  may  be  able  to  come  back  to  the  work  in  the  old  spirit 
and  with  renewed  vigor.  In  addition  to  the  meeting  last  May,  when 
the  students  of  the  graduating  class  presented  abstracts  of  their 
theses,  there  have  been  three  other  meetings  held.  The  first  of  these 
was  in  October,  when  Professor  Eugene  Charabot,  of  Paris,  gave  a 
charming  address  in  French  on  "  The  Formation  and  Distribution 
of  Odorous  Products  in  Plants."  This  was  rather  a  unique  occasion 
in  that  a  large  number  of  students  were  present  and  nearly  every 
one  expressed  delight  in  the  privilege  of  hearing  this  discourse.  The 
article  was  printed  in  full  in  the  Journal,  translation  having  been 
made.  He  also  stated  that  he  had  just  received  a  request  from  the 
editor  of  a  Hungarian  periodical  to  reprint  the  address. 

Another  meeting  was  held  in  November.  Professor  La  Wall 
had  an  article  on  the  "  Detection  of  Chicory  in  Decoctions  of  Chicory 
and  Coffee."  This  paper  caused  a  great  deal  of  interest,  and  was 
published  in  full  in  the  Journal.  Mr.  Boring  exhibited  several 
specimens  of  elixir  of  iron,  quinine,  and  strychnine,  and  Professor 
Remington  gave  an  illustrated  lecture  on  "  Some  Pharmaceutical 
Celebrities  I  Have  Met  " ;  also  touching  on  the  pharmaceutical  col- 
leges and  the  professional  aspect  of  pharmacy  in  Europe,  especially 
England  and  Germany. 

The  third  meeting  was  held  in  February,  when  Mr.  Lobeck 
gave  a  talk  on  "  A  Roughing  Trip  Across  the  Continent,"  illustrated 
with  colored  photographs.  It  was  a  very  practical  talk  not  only  on 
how  one  should  arrange  a  vacation,  but  to  get  the  most  out  of  it. 

Editor's  Report,  read  by  Professor  Kraemer.  During  the  past 
year  we  have  published  572  pages,  exclusive  of  a  10-page  index. 
This  matter  included  75  original  and  selected  papers  covering  a  wide 


228  Philadelphia  College  of  Pharmacy.  {A%a°%iJar,n- 

range  of  subjects  relating  to  pharmacy.  We  have  received  the 
support  of  investigators  in  various  parts  of  the  United  States  and 
those  connected  with  other  colleges ;  our  own  members  continue 
to  contribute  articles  and  in  other  ways  promote  the  objects  of  the 
Journal.  The  following  graduates  have  contributed  articles  during 
the  year:  George  M.  Beringer,  George  M.  Beringer,  Jr.,  Dr.  Robert 
A.  Hatcher,  Victor  O.  Homerberg,  Henry  Kraemer,  Professor 
Charles  H.  La  Wall,  Dr.  Frederick  B.  Power,  Sister  Bertha  Muller, 
Professor  Joseph  P.  Remington,  John  R.  Rippetoe,  John  K.  Thum 
and  M.  I.  Wilbert,  and  from  the  Honorary  Members :  Professor 
Charles  E.  Bessey,  Professor  W.  G.  Farlow,  Professor  A.  Tschirch 
and  Dr.  A.  L.  Winton. 

The  Quarterly  Report  on  Progress  in  Pharmacy,  by  M.  I.  Wil- 
bert, continues  to  be  one  of  the  important  features  of  the  Journal, 
as  it  gives  an  excellent  resume  of  discoveries  of  interest  to  medicine 
and  important  happenings  in  pharmacy.  During  the  past  year  we 
have  published  a  number  of  general  articles  which  have  given  in  a 
nutshell  some  of  the  advances  in  modern  science.  Among  these 
articles  we  mention  Ehrlich's  Chemical  Therapy,  Phylacogens,  Col- 
loids and  Crystals,  Enzymes,  and  Phenomenon  of  Catalysis. 

Curator's  Report,  read  by  J.  W.  England.  The  Museum  of 
the  College  is  growing  yearly  in  importance.  The  entire  collection 
of  drugs  and  drug  products  and  the  Martindale  Herbarium  should 
be  relabelled.  The  containers  for  the  drugs  should  be  standardized 
to  two  sizes  only.  The  Museum  could  be  made  more  valuable  to  the 
pharmaceutical  public  as  a  place  of  reference  for  standard  or  typical 
drugs  and  drug  products,  and  most  interesting  also  to  the  general 
public,  if  the  historical  collections  were  properly  displayed.  The 
Museum  consists  in  large  part  of  typical  specimens  of  rare  drugs. 
It  should  be  improved  by  the  addition  of  typical  specimens  of  the 
more  commonly  used  drugs  as  well,  and  especially  by  a  proper  dis- 
play of  our  historical  matter  and  apparatus. 

The  recommendations  and  suggestions  in  the  Curator's  report 
were,  on  motion,  referred  to  the  Board  of  Trustees. 

Librarian's  Report,  read  by  Professor  Sadtler.  During  the 
year  the  Library  has  added  by  purchase,  gifts,  and  exchanges  a 
total  of  105  volumes,  80  volumes  of  periodicals  and  theses  have  been 
bound,  2384  books  have  been  accessioned,  classified,  and  shelf- 
listed,  making  a  total  of  7264  books  ready  to  be  catalogued.  Use 


Am  Ma°y  ri9i4arm' }    Philadelphia  College  of  Pharmacy.  229 

of  Library  during  the  year  by  1375  persons,  an  increase  of  378  over 
last  year. 

The  report  of  the  Committee  on  Nominations  was  read  and 
ordered,  entered  and  filed. 

A  communication  was  read  from  C.  Carroll  Meyer,  declining  the 
nomination  for  membership  in  the  Board  of  Trustees  because  of 
pressure  of  business  preventing  his  attendance  at  the  meetings. 

The  President  appointed  Professor  F.  X.  Moerk,  Mitchell  Bern- 
stein and  E.  H.  Hessler  tellers,  to  conduct  the  election.  The  report 
of  the  Committee  on  Nominations  being  again  read,  the  members 
proceeded  to  a  ballot.  While  the  ballots  were  being  counted,  Pro- 
fessor Stroup  alluded  to  a  recent  notice  received  from  the  Fire 
Marshal  and  quoting  an  Act  of  Assembly  prohibiting  smoking  in  any 
part  of  the  building.  He  hoped  there  would  be  some  modification  of 
the  rule  so  as  to  permit  smoking  in  the  corridor,  which  was  entirely 
fireproof.  Past  experience  had  shown  that  when  prohibition  was  en- 
forced the  entrance  and  the  street  in  front  of  the  College  were  used 
as  a  place  for  smoking  and  a  number  of  complaints  and  police 
troubles  had  resulted.  A  number  of  the  members  related  various 
experiences,  viz.,  President  French,  Professors  Remington,  Kraemer, 
Sadtler,  Lowe,  Messrs.  Beringer  and  Poley;  the  speakers  generally 
thinking  that,  while  protection  from  the  risks  of  fire  was  absolutely 
necessary,  some  means  should  be  devised  to  permit  smoking  in  some 
part  of  the  building.  The  discussion  was  closed  by  President  French 
stating  he  would  confer  with  Director  Porter  regarding  the  matter. 

The  tellers  reported  the  results  of  the  election  as  follows : 

President,  Howard  B.  French ;  first  vice-president,  R.  V.  Matti- 
son,  M.D. ;  second  vice-president,  J.  L.  Lemberger;  treasurer,  Rich- 
ard M.  Shoemaker;  corresponding  secretary,  A.  W.  Miller,  M.D. ; 
recording .  secretary,  C.  A.  Weidemann,  M.D. ;  curator,  Joseph  W. 
England ;  editor,  Henry  Kraemer ;  librarian,  Katharine  E.  Nagle ; 
trustees  for  three  years :  Joseph  P.  Remington,  C.  Stanley  French, 
George  B.  Evans ;  Publication  Committee :  Samuel  P.  Sadtler,  Henry 
Kraemer,  Joseph  P.  Remington,  Joseph  W.  England,  Martin  I. 
Wilbert,  Charles  H.  La  Wall,  and  John  K.  Thum;  Committee  on 
Pharmaceutical  Meetings :  Henry  Kraemer,  Joseph  P.  Remington, 
C.  B.  Lowe,  George  B.  Weidemann,  and  E.  H.  Hessler. 

The  President  declared  the  above  duly  elected. 

The  President  made  the  following  appointments : 


230  Minutes  of  Board  of  Trustees.       {  A%Ja7,\9u.arm' 

Committee  on  By-Laws :  George  M.  Beringer,  Joseph  W.  Eng- 
land, and  C.  A.  Weidemann. 

Delegates  to  the  Pennsylvania  Pharmaceutical  Association :  C. 
B.  Lowe,  Joseph  P.  Remington,  F.  P.  Stroup,  O.  W.  Osterlund, 
William  E.  Lee,  Charles  H.  La  Wall,  and  E.  Fullerton  Cook. 

Delegates  to  New  Jersey  Pharmaceutical  Association :  Henry 
Kraemer,  George  M.  Beringer,  C.  B.  Lowe,  Charles  H.  La  Wall,  and 
H.  P.  Thorn. 

Delegates  to  Delaware  Pharmaceutical  Association :  A.  W.  Miller, 
M.D.,  C.  B.  Lowe,  and  H.  J.  Watson. 

The  President  announced  the  death  of  David  H.  Ross  on  Jan- 
uary 26,  1 9 14.    He  joined  the  College  in  1888. 

William  M.  Morrison  presented  an  old  scale  and  two  cases  of  in- 
struments originally  owned  by  Dr.  Stott,  who  died  in  1837.  The 
thanks  of  the  College  were  tendered  the  donor. 

C.  A.  Weidemann,  M.D., 

Recording  Secretary. 


ABSTRACTS  FROM  THE  MINUTES  OF  THE 
BOARD  OF  TRUSTEE'S. 

December  2,  1913. — Sixteen  members  present. 

Committee  on  Library  reported  total  number  of  books  accessioned 
to  date  5449.  A  number  of  books  were  purchased  during  the  month 
and  the  Library  was  used  by  154  persons. 

A -communication  from  the  Board  of  Public  Education  was  read, 
recommending  that  Miss  Florence  McGarrity  be  awarded  a  scholar- 
ship ;  and,  on  motion,  the  recommendation  was  approved. 

An  application  for  active  membership  was  received  from  a 
graduate  of  the  1913  class,  now  a  resident  of  China,  and,  as  usual,  it 
was  referred  to  the  Committee  on  Membership. 

The  Treasurer  reported  that  on  November  8th  Mrs.  Anna  Shinn 
Maier  sent  her  check  for  $2000  to  establish  a  scholarship  in  memory 
of  her  father,  James  T.  Shinn,  the  income  from  said  amount  to  be 
devoted  for  scholarship  purposes.  On  motion,  it  was  voted  that  the 
Treasurer  convey  the  thanks  of  the  College  to  Mrs.  Maier. 

January  6,  1914. — Fifteen  members  present. 

Committee  on  Property  reported  the  change  from  white  to  green 


Am'MJa°yri9i4ftrm' }       Minutes  of  Board  of  Trustees.  231 

shades  in  the  electric  light  over  the  lecture  table  in  the  Materia 
Medica  room. 

A  petition  signed  by  75  per  cent,  of  the  students  relative  to  the 
establishment  of  a  lunch  room  in  the  College  building  was  submitted 
by  the  Property  Committee.  The  Dean  explained  in  detail  the 
reasons  that  prompted  the  presenting  of  the  petition  by  the  students, 
and  advocated  the  adoption  of  a  plan  complying  with  their  request. 
After  some  discussion  it  was  moved  that  the  Board  approve  the 
plan  if  the  Committee  on  Property  found  that  same  could  be  put  in 
operation  without  the  College  being  compelled  to  assume  any  respon- 
sibility.   It  was  so  ordered. 

Committee  on  Library  reported  476  books  accessioned  and  shelf- 
listed  during  the  month.  A  number  of  books  had  been  donated  and 
190  persons  had  used  the  Library  during  the  month. 

Committee  on  Accounts  and  Audit  reported  they  had  examined 
the  accounts  of  the  Treasurer,  Registrar,  and  the  American  Jour- 
nal of  Pharmacy,  and  found  them  correct. 

Committee  on  Announcement  reported  the  publication  of  the 
December  issue  of  the  Bulletin,  that  Pharmacy  Talk  No.  1  had  been 
sent  out,  and  that  they  had  in  preparation  a  series  of  8  "  Talks  " — 
one  to  be  issued  each  month. 

The  Corresponding  Secretary  of  the  College  read  several  letters 
from  those  who  were  recently  elected  to  Honorary  Membership  in 
the  College. 

The  Committee  on  Membership  having  reported  favorably  on 
the  application  of  Mr.  Job  Fong,  of  Canton,  China,  for  active  mem- 
bership, a  ballot  was  taken  and  he  was  unanimously  elected. 

February  3,  1914. — Fourteen  members  present. 

Committee  on  Property  reported  that  inquiries  had  been  made 
and  it  was  found  to  be  possible  to  make  arrangements  with  a  caterer 
to  serve  a  light  lunch  in  the  College  building  for  the  accommodation 
of  the  students.  On  motion,  the  matter  was  referred  to  the  Com- 
mittee on  Property  with  power  to  act. 

Committee  on  Library  reported  that  454  books  were  accessioned 
during  the  month,  making  a  total  of  6378  books  ready  to  be  cata- 
logued.  The  Library  was  consulted  by  143  persons. 

Committee  on  Instruction  reported  progress  concerning  matters 
that  they  had  had  under  consideration. 

The  Chair  announced  that  Dr.  P.  S.  Stout  had  been  requested 
to  present  a  report  of  the  Alumni  Special  Committee  having  in 


232 


President's  Address. 


Am.  Jour.  Pharm. 
May,  1914. 


charge  the  Centennial  Fund,  and  asked  that  the  regular  order  of 
business  be  suspended.  This  being  agreed  to,  Dr.  Stout  was  intro- 
duced and  presented  a  detailed  report  of  what  had  been  done  up  to 
this  time.  The  main  object  of  the  movement  is  to  obtain  by  sub- 
scription and  bequest,  as  may  be  most  acceptable  to  the  donor,  a 
fund  of  $500,000  or  more,  to  be  devoted  to  improvements — location, 
building,  equipment,  etc.,  and  to  the  establishment  of  an  endowment 
for  the  College.  The  action  of  the  committee  was  endorsed,  and 
the  Board  gave  assurance  of  furthering  the  movement  in  every  way 
possible.  ;  :   M  i  j  Jul 

Committee  on  Examinations  reported  they  had  been  engaged  for 
several  months  in  formulating  a  set  of  rules  for  regulating  the  con- 
duct of  examinations  in  the  College.  A  number  of  recommendations 
were  submitted  and  extended  discussion  followed.  As  this  was  an 
important  matter,  it  was  voted  that  further  consideration  of  the 
subject  be  deferred  to  an  adjourned  meeting  to  be  held  February  9th. 

The  Dean  presented  the  form  of  certificate  which  the  Board  had 
some  months  before  referred  to  a  Special  Committee  for  considera- 
tion, covering  special  branches  of  study.  The  form  met  with 
approval,  and  it  was  voted  that  certificates  be  finished  in  accordance 
with  the  outlines  proposed. 

An  application  for  active  membership  was  received  and  referred 
to  the  appropriate  committee. 

February  9,  1914. — Eleven  members  present. 

This  meeting  was  called  to  give  further  consideration  to  the  re- 
port of  the  Committee  on  Examinations.  After  an  extended  dis- 
cussion, participated  in  by  many  of  the  members,  action  was  deferred. 


PRESIDENT'S  ADDRESS.1 
To  the  Members  of  the  Philadelphia  College  of  Pharmacy: 

Your  President  has  pleasure  in  submitting  at  this  time,  in  ac- 
cordance with  his  established  practice,  a  brief  summary  of  matters 
of  general  interest  relating  to  your  institution. 

The  College  buildings  at  the  present  time  are  in  good  condition. 
The  walls  and  ceiling  of  the  library  have  been'  painted,  the  floor 
covered  with  a  cork  carpet,  and  new  chairs  provided.  The  walls  of 
the  back  stairway  have  been  coated  with  a  light-colored  paint, 
which  has  proven  of  advantage  in  brightening  up  this  portion  of 

1  In  abstract. 


Am.  Jour.  Pharm. 
May,  1914. 


President's  Address. 


233 


the  building.  Alterations  were  made  in  the  third-floor  Microscopical 
Laboratory,  giving  greater  facilities  for  the  revised  and  expanded 
course  in  Bacteriology,  which  is  now  an  obligatory  course  in  charge 
of  Prof.  John  A.  Roddy.  Changes  have  also  been  made  in  Alumni 
Hall  for  the  benefit  of  the  classes  in  Microscopy. 

Following  the  approval  of  the  Board  of  Trustees  of  a  petition 
signed  by  a  number  of  the  students,  asking  that  a  lunch-room  be 
established,  a  lunch  counter  was  started  a  few  weeks  ago  and  is 
being  continued  with  increasing  success.  The  lunches  furnished 
are  substantial  and  wholesome,  and  from  the  patronage  received  it 
would  appear  that  the  students  in  general  appreciate  the  innovation. 
The  Property  Committee  will,  no>  doubt,  £nd  it  necessary,  in  the 
near  future,  to  enlarge  the  facilities  for  this  purpose,  as  the  present 
accommodations  are  not  equal  to  the  demand. 

The  total  number  of  students  in  attendance  at  the  College  at  this 
time  is  434,  an  increase  of  fourteen  over  last  year.  Of  the  number 
mentioned,  145  are  first-year  students,  109  second-year  students, 
141  third-year  students,  38  special  chemistry  students,  and  1  student 
taking  the  Food  and  Drug  course.  There  were  168  first-year 
matriculants — 167  regulars  and  1  special.  Of  this  number,  1  student 
is  deceased  and  22  are  not  attending.  The  second-year  matriculants 
numbered  113 — 112  regulars  and  1  special.  Of  this  number,  4  are 
not  attending.  There  were  124  regular  third-year  matriculants  and 
18  students  remaining  from  class  of  1912-13.  Of  the  total  of  142 
third-year  students,  1  is  not  attending. 

Of  those  seeking  admittance  to  the  College  at  the  beginning 
of  the  fall  term,  29  applicants  were  not  able  to  furnish  satisfactory 
entrance  credentials.  These  were  given  the  privilege  of  remaining 
at  the  College  and  repeating  the  first-year  work  during  1914-15,  in 
the  meantime  being  expected  to  qualify.  A  few  of  the  number  have 
availed  themselves  of  this  privilege,  but  of  these  'only  four  are 
attending  at  the  present  time,  and  under  the  circumstances  are  not 
listed  as  students. 

In  the  department  of  Analytical  Chemistry,  13  first-year,  28 
second-year,  and  35  third-year  students  have  been  doing  special 
work.  Of  the  number  of  third-year  students  mentioned,  9  are 
doing  thesis  work.  Twenty-five  students  are  taking  the  special 
laboratory  course  in  Bacteriology;  of  this  number,  7  are  specials 
and  18  regulars.  Fourteen  of  the  special  Chemistry  students  are 
availing  themselves  of  the  special  course  in  Microscopy ;  and  10 


234  President's  Address.  {Am'Ma0y,ri9Pi4arm' 

students  are  doing  special  work  in  the  Microscopical  Laboratory,  in 
connection  with  their  theses. 

The  work  in  the  Department  of  Pharmacy  for  the  course  of 
1914-1915  is  being  successfully  carried  on. 

The  recording  of  the  attendance,  as  now  required  by  the  State 
Pharmaceutical  Board,  has  been  of  considerable  value,  and  resulted 
in  a  higher -grade  of  scholarship  being  attained  by  the  classes. 

The  extra  lectures  on  pharmaceutical  subjects  given  during 
the  college  courses  have  been  of  material  value  and  more  largely 
attended. 

The  course  in  Commercial  Training,  under  the  control  of  the 
Department  of  Pharmacy,  and  for  which  the  students  are  not 
charged,  has  been  greatly  increased;  the  number  of  hours  devoted 
to  this  branch  has  been  doubled  since  last  year.  Illustrative 
material  is  fully  shown,  bookkeeping  methods  are  compulsory,  and 
students  are  now  required  to  keep  an  individual  set  of  books  and 
submit  them  for  examination. 

The  Department  of  Botany  and  Pharmacognosy  has  given  evi- 
dence of  considerable  advancement  during  the  past  year.  A  special- 
ized course  in  Microscopy  has  been  developed,  giving  the  special 
chemistry  students  enlarged  opportunities  for  increasing  their  effi- 
ciency and  broadening  their  powers  as  analysts.  The  course  com- 
prises a  series  of  laboratory  periods  on  Saturday  mornings  and 
includes  a  wide  range  of  topics,  namely,  the  study  of  drugs,  foods, 
and  technical  products  with  their  deterioration  and  adulteration. 
The  large  number  of  specimens  bearing  upon  this  work,  which  your 
Professor  of  Botany  and  Pharmacognosy  and  his  assistants  have 
been  diligently  collecting  for  a  number  of  years,  is  now  being 
brought  into  practical  use,  and  is  proving  of  great  advantage. 

It  is  of  interest  to  note  the  increasing  demand  among  agricultural 
experiment  stations  and  the  government  laboratories  for  pharma- 
cognocists  or  thoroughly  trained  analysts ;  and  as  microscopical 
courses  are  not,  as  a  rule,  included  with  chemical  courses  given  in 
this  country,  the  Philadelphia  College  of  Pharmacy,  in  the  establish- 
ment of  such  a  course,  will  undoubtedly  be  enabled  to  prepare 
students  of  chemistry  for  a  broader  knowledge  and  a  deeper  under- 
standing of  the  intricacies  of  the  work  they  have  elected,  thus 
extending  the  educational  prestige  of  the  College. 

The  greenhouse  and  roof  garden  continue  to  furnish  the  students 
in  Botany  and  Pharmacognosy  facilities  for  growing  plants  and  con- 
ducting special  investigations. 


Am.  Jour.  Pharm. 
May,  1914. 


President's  Address. 


235 


In  the  Department  of  Materia  Medica  the  Physiological  assay  of 
drugs  has  been  given  increased  attention,  with  good  results.  Your 
Medical  Examiner  reports  that  the  physical  examination  of  your 
students  is  somewhat  hampered  by  lack  of  sufficient  light.  It  may, 
therefore,  be  necessary  for  your  Committee  on  Property  to  install 
a  special  light  for  this  purpose  in  the  near  future. 

On  Thursday  evening,  May  22,  191 3,  the  92nd  Annual  Com- 
mencement exercises  of  your  College  were  held  in  the  Academy  of 
Music.  The  graduating  class  numbered  123,  representing  22  States 
of  the  Union,  District  of  Columbia,  Canada,  China,  and  Russia. 

During  the  past  year  the  College  has  received  from  Mrs.  Anna 
Shinn  Maier,  daughter  of  your  late  treasurer,  James  T.  Shinn,  a 
sum  sufficient  to  convert  the  Shinn  Memorial  into  a  scholarship. 

The  Pennsylvania  Scholarship  Fund  of  $2500  is  nearing  com- 
pletion ;  $2200  has  been  collected. 

There  are  at  present  148  active  members  of  your  College,  and 
13  associate  members.  During  the  year  6  active  members  and  1 
associate  member  were  elected.  The  resignation  of  one  active  mem- 
ber was  received;  and  your  President  regrets  to  report  the  death 
of  three  of  your  active  members  during  the  year,  as  follows : 

John  W.  Ridpath,  May  8,  191 3.   Joined  the  College  in  1888. 

Evan  T.  Ellis,  September  29,  1913.   Joined  the  College  in  1852. 

David  H.  Ross,  January  26,  1914.    Joined  the  College  in  1879. 

It  is  of  interest  to  note  that  Evan  T.  Ellis  was  the  oldest  member 
of  the  College. 

It  is  thought  desirable  by  your  President  to  bring  to  your  atten- 
tion the  fact  that  the  Department  of  Public  Safety  of  Philadelphia, 
recognizing  the  danger  incident  to  smoking  in  buildings  where 
people  are  assembled  in  numbers  on  various  floors,  deemed  it 
necessary  to  send  a  communication  to  your  College,  reading  as 
follows : 

Mr.  Howard  B.  French,  President, 
Philadelphia  College  of  Pharmacy, 
145  No.  10th  Street, 
Philadelphia. 

Dear  Sir: 

Complaint  has  been  made  to  this  Bureau  of  the  promiscuous  smoking 
of  cigarettes  and  cigars  in  the  building  of  the  College  of  Pharmacy. 

The  Fire  Marshal  has  made  an  inspection  of  the  complaint  and  considers 
it  of  vital  importance  that  the  practice  be  discontinued  at  once. 


236  President's  Address.  { Am-  J°auyr; 

I  therefore  request  that  proper  notices  be  placed  in  all  parts  of  the 
building  where  there  are  no  tile  or  cement  floors,  in  order  that  those  offend- 
ing may  have  knowledge  of  the  fact  that  it  is  in  violation  of  the  Act  of 
Assembly. 

I  would  appreciate  it  if  you  would  give  this  the  publicity  it  deserves. 

Yours  very  truly, 

(Signed)     Geo.  D.  Porter, 

Director. 

The  body  of  this  communication  has  been  printed  and  promi- 
nently displayed  throughout  your  buildings;  and  it  is  earnestly 
hoped  that  students  in  the  College  will  respect  said  notice  by  dis- 
continuing the  practice  of  smoking  in  the  portions  of  the  buildings 
where  there  are  no  tile  or  cement  floors,  and  that  arbitrary  measures 
to  enforce  the  order  may  not  be  found  necessary. 

Your  President  wishes  to  call  attention  to  the  fact  that  on  the 
21st  of  March,  1921,  the  College  will  have  attained  the  one  hun- 
dredth anniversary  of  its  existence.  This  is  but  seven  years  away, 
and  your  President  desires  to  urge  upon  all  members  of  the  College 
the  desirability  of  collecting  and  placing  in  possession  of  the  College 
any  historical  matters  they  may  have  or  may  be  able  to  obtain.  He 
would  suggest  that  old  prescription  labels  and  labels  referring  to 
specific  preparations  could  be  readily  collected  from  time  to  time 
from  many  of  the  old  drug  stores,  and  would  prove  of  much  interest. 
He  also  hopes  that  a  strenuous  effort  may  be  made  to  collect 
as  many  of  the  old-time  appliances  as  possible.  It  is  the  earnest 
hope  of  your  President  that  when  celebrating  the  100th  birthday 
of  the  College  there  may  be  an  historical  exhibition  at  that  time  that 
will  not  only  attract  the  attention  and  interest  of  the  pharmacists 
throughout  the  country,  but  of  members  of  the  medical  and  allied 
professions. 

In  closing,  your  President  desires  to  express  appreciation  to 
those  of  the  officers  and  faculty  who  have  so  heartily  cooperated 
with  him  during  the  past  year;  and  to  those  who  have  not  been 
in  full  accord  with  his  views,  he  wishes  to  express  the  hope  that 
all  personal  feelings  may  be  put  aside  and  that  a  united  effort  may 
be  made  to  continue  the  prosperity  and  advancement  of  this  institu- 
tion, which  is  dear  to  the  hearts  of  all  those  associated  with  it. 

Howard  B.  French. 

March  30,  1914. 


Am.  Jour.  Pharm. 
May,  1914. 


The  Vitamines. 


237 


THE  VITAMINES.1 

The  Recognition  oe  Essential  Constituents  of  the  Diet 
Hitherto  Unclassified — Deficiency  Diseases. 

By  Percy  G.  Stiles. 

If  a  physiologist  is  asked  what  are  the  requisites  of  a  normal  diet 
he  will  probably  reply  somewhat  as  follows :  First,  it  must  represent 
an  adequate  quantity  of  available  potential  energy,  not  less  than 
2,000  calories  for  the  average  human  adult.  Second,  it  must  contain' 
protein  (nitrogenous)  food  sufficient  to  compensate  for  the  un- 
avoidable daily  loss  of  similar  material  from  the  body.  Third,  it 
must  be  palatable  and  digestible,  making  due  allowance  for  personal 
idiosyncrasy.  He  will  very  probably  content  himself  with  these 
three  postulates. 

If  the  inquiry  is  pressed  the  man  of  science  may  recollect  that 
another  necessary  condition  of  successful  nutrition  is  a  proper 
supply  of  the  inorganic  or  mineral  elements  in  sufficiently  varied 
assortment.  The  tissues  cannot  be  developed  or  maintained  without 
chlorides,  phosphates,  and  other  saline  contributions.  The  need  for 
substances  of  this  class  is  more  urgent  during  the  period  of  growth 
than  later,  but  it  always  continues  to  exist.  A  similar  statement  may 
be  made  with  reference  to  the  protein  of  the  ration ;  this,  too,  must 
be  furnished  in  relative  abundance  and  varied  form  during  the 
growth  of  the  subject  and  may  be  reduced  when  full  stature  has 
been  reached.  Mendel  has  shown  that  kind  as  well  as  quantity 
must  be  considered  when  protein  is  chosen  for  experimental  nutri- 
tion of  an  animal.  Proteins  from  certain  sources  suffice  for  main- 
tenance only  and  not  to  minister  to  growth. 

With  the  accumulation  of  physiological  data  during  the  past 
few  years  it  has  become  increasingly  apparent  that  there  may  be 
criteria  for  the  adequacy  of  a  diet  not  included  in  the  list  just  given. 
There  are  now  known  to  be  organic  compounds  other  than  proteins, 
small  quantities  of  which  are  absolutely  essential  to  normal  growth 
and  even  to  continued  health  in  the  adult  condition.  The  name  of 
Vitamines  has  been  proposed  for  all  such  substances.  The  word 
is  well  chosen  in  view  of  its  root-meaning ;  an  amine  is  a  nitrogenous 
compound  of  a  certain  type  and  a  vitamine  is  obviously  such  a 


1  Reprinted  from  Science  Conspectus,  Vol.  IV,  1914,  pp.  10-13. 


238 


The  V  it  amines. 


Am.  Jour.  Pharm. 
May,  1914. 


compound  with  the  added  distinction  of  being  necessary  to  life. 
Casimir  Funk  of  London  has  been  one  of  the  foremost  contributors 
to  the  development  of  this  conception  and  a  valuable  summary  of 
his  own  work  and  his  judgment  of  the  work  of  others  may  be  found 
in  the  Ergebnisse  der  Physiologie,  Vol.  XIII,  pp.  124-205.  (Wies- 
baden, 1913.)    This  article  is  the  chief  source  of  the  present  abstract. 

A  class  of  serious  disorders  has  long  been  known  in  which 
failure  of  nutrition  could  be  named  as  the  cardinal  fact  in  the  case 
and  in  which  it  has  somewhat  vaguely  been  assumed  that  the  diet 
must  be  at  fault.  The  most  familiar  disturbance  of  this  class,  at 
least  to  the  general  reader,  has  probably  been  scurvy.  The  chronicles 
of  exploring  expeditions  in  polar  regions  have  contained  many  har- 
rowing accounts  of  the  ravages  of  this  disease.  It  has  usually  been 
associated  with  the  consumption  of  a  monotonous  ration,  deficient 
in  fresh  vegetables  and  often  containing  a  great  deal  of  salted  or 
canned  food.  Certain  supplementary  articles  of  diet,  such  as  onions, 
limes,  and  lemons,  have  been  credited  with  some  power  to  ward  off 
or  at  least  to  mitigate  the  trouble  and  they  have  been  spoken  of 
as  antiscorbutics. 

The  victims  of  scurvy  suffer  from  severe  prostration,  loosening 
of  the  teeth,  intense  soreness  of  the  gums,  friability  of  the  bones, 
and  a  tendency  to  haemorrhage  partly  due  to  a  loss  of  the  coagulating 
property  of  the  blood.  Those  who  have  read  the  classic  journals  of 
Doctor  Kane  will  recall  the  distressing  situation  on  board  his  ship 
at  the  end  of  the  Arctic  winter  and  the  commander's  device  to 
cheer  his  helpless  men  in  the  forecastle  by  setting  up  a  mirror  to 
bring  into  their  midst  the  first  sunbeam  from  the  southern  horizon. 
Scurvy  has  become  less  common  with  better  supplies  of  food  avail- 
able for  such  parties,  but  it  has  been  noted  within  a  very  few  years. 

Another  disorder  which  has  lately  attracted  much  attention  is 
beri-beri.  It  has  its  recognized  centre  in  the  East,  particularly  in 
Japan,  China,  Indo-China,  and  the  Philippines.  Its  occurrence  in 
Newfoundland  has  recently  been  reported.  Those  who  suffer  from 
beri-beri  are  usually  the  very  poor  and,  in  the  Orient  at  least,  they 
are  people  who  live  chiefly  upon  rice.  In  Japan  the  disease  has  been 
nearly  eliminated  from  the  army  and  navy  by  providing  more  liberal 
and  varied  rations.  The  symptoms  are  complex,  but  they  are  in 
general  such  as  can  be  referred  to  the  impairment  of  the  nerves, 
which  is  known  to  be  the  most  prominent  physical  change.  There 
is  a  period  of  declining  weight  and  strength  and  this  is  followed  by 


Am.  Jour.  Pharm.  > 
May,  1914.  J 


The  Vitamines. 


239 


the  development  of  a  "  multiple  neuritis  "  with  partial  paralysis  in 
both  the  motor  and  the  sensory  realms. 

Various  theories  have  been  held  with  regard  to  beri-beri.  It 
has  been  believed  to  be  an  infectious  disease  because  it  so  often 
affects  a  large  number  of  people  who  are  closely  associated,  as  in 
a  prison,  a  ship,  or  a  laborers'  camp.  The  fact  was  formerly  over- 
looked that  such  companies  share  the  same  diet  and  that  their 
trouble  may  well  be  due  to  that  source.  This  is  now  accepted  as 
proved.  But  when  the  decision  is  reached  that  something  must  be 
wrong  with  the  food  there  are  still  two  possible  views  to  be  con- 
sidered. Is  the  diet  positively  poisonous  or  is  it  merely  insufficient? 
This  question  has  been  asked  both  with  reference  to  scurvy  and  to 
beri-beri.  It  is  not  easy  to  answer  it  in  such  a  way  as  to  meet  all  ob- 
jections. Nevertheless,  the  tendency  is  toward  the  conclusion  that 
it  is  the  inadequacy  rather  than  the  toxic  nature  of  the  food  which 
is  to  be  held  responsible  in  these  and  perhaps  in  other  cases. 

It  is  proposed  to  call  such  failures  of  nutrition  "  deficiency 
diseases."  It  is  assumed  that  the  lack  is  of  one  or  more  of  the 
specific  substances  already  termed  vitamines.  The  evidence  in 
support  of  such  a  conception  is  especially  convincing  in  the  case  of 
beri-beri.  As  long  ago  as  1897  it  was  discovered  that  rice  which  has 
been  "  polished  " — that  is,  deprived  of  its  pericarp  or  immediate 
husk — has  a  tendency  to  induce  beri-beri  and  that  the  inclusion  of 
the  pericarp  makes  it  entirely  wholesome.  It  has  been  possible  to 
confirm  this  in  a  striking  manner  by  experiments  on  birds.  If  a 
fowl  or  a  pigeon  is  restricted  to  polished  rice  as  a  diet  it  soon  re- 
fuses to  eat.  If  forced  feeding  is  then  resorted  to  it  soon  becomes 
pitiably  weak  and  cannot  long  survive.  The  partial  feeding  is  thus 
as  surely  destructive  as  absolute  starvation.  Post-mortem  study  of 
such  birds  shows  marked  degeneration  of  the  nerves.  The  service 
of  the  pericarp  may  be  conceived  of  in  either  of  two  ways.  The 
polished  rice  may  contain  an  active  poison  for  which  the  husk  pro- 
vides a  natural  antidote.  The  alternative  is  that  the  pericarp 
furnishes  a  necessary  constituent  of  the  nerve  tissue,  a  vitamine,  for 
want  of  which  the  nerve-fibres  deteriorate.  How  hard  it  is  to  choose 
between  these  two  views  has  already  been  suggested. 

Funk  has  been  successful  in  his  patient  endeavor  to  isolate 
the  vitamine  the  lack  of  which  causes  beri-beri.  He  has  obtained 
from  the  pericarp  of  rice  a  number  of  fractions,  only  one  of  which 
has  the  remedial  property.    This  appears  to  be  a  definite  organic 


240 


The  V  it  amines. 


Am.  Jour.  Pharm. 
May,  1914. 


body  to  which  a  formula  can  be  assigned.  It  contains  nitrogen  but 
not  phosphorus,  an  element  which  earlier  workers  had  believed  to 
be  concerned.  The  vitamine  can  be  separated  from  other  foods 
than  rice.  Various  animal  tissues  yield  it  and  so  do  certain  veg- 
etables. Any  kind  of  food  which  contains  the  vitamine  may  be 
used  to  supplement  a  ration  of  polished  rice  with  the  result  that  it 
becomes  sufficient  for  the  maintenance  of  the  animal.  Yolk  of  egg 
and  yeast  are  said  to  have  the  curative  power  in  the  highest  degree. 

It  is  interesting  to  follow  Funk's  conjectures  as  to  the  systemic 
effects  of  the  withholding  of  the  invaluable  vitamine.  We  know 
that  in  starvation  the  organs  which  cannot  be  spared  are  sustained  at 
the  expense  of  others.  The  heart  and  the  nervous  system  have  been 
found  to  keep  their  full  weight  to  the  last  while  tissues  which  are 
less  necessary  to  the  continuance  of  life  are  greatly  reduced.  Even 
the  bones  are  levied  upon  to  the  extent  of  one-sixth  of  their  mass. 
We  may  expect  to  see  the  same  principle  illustrated  in  the  partial 
starvation  which  is  at  the  root  of  any  deficiency  disease. 

So  in  beri-beri.it  may  be  supposed  that  the  vitamine  which  is 
absolutely  essential  to  the  normal  nervous  system  is  not.  at  first  con- 
fined to  that  part  of  the  body.  The  feeding  experiments  have  given 
evidence  that  it  is  present  in  the  muscles  though  rather  scantily. 
It  is  to  be  expected  that  in  the  event  of  failure  of  a  supply  direct 
from  the  diet  the  muscles  will  be  made  to  surrender  their  store  of 
the  vitamine  to  replace  that  which  has  been  destroyed  in  the  nervous 
tissues.  If  we  are  to  think  that  the  vitamine  is  essential  to  the 
muscles  as  well  as  to  the  nerves  we  shall  anticipate  that  its  with- 
drawal will  result  in  a  disintegration  of  the  muscle  .protoplasm 
quite  out  of  proportion  to  the  small  amount  of  vitamine  yielded  to 
the  preferred  creditor.  So  for  a  while  there  will  be  loss  of  weight 
and  strength  but  no  marked  nervous  symptoms  because  the  nerves 
are  being  kept  in  condition  at  the  cost  of  a  remorseless  sacrifice 
of  the  other  tissues.  When  the  internal  supply  ceases  to  be  suffi- 
cient the  acute  nervous  effects  are  at  once  developed. 

It  is  the  opinion  of  Funk  that  both  beri-beri  and  scurvy  are 
prevented  by  the  liberal  use  of  potatoes.  Before  this  vegetable 
was  introduced  into  Europe  there  were  severe  epidemics  which  are 
believed  to  have  been  outbreaks  of  scurvy.  The  suggestion  that 
the  potato  should  now  be  added  to  the  food-supply  of  the  eastern 
countries  in  which  beri-beri  is  prevalent  seems  a  wise  one.  But 
the  fact  is  to  be  emphasized  that  almost  any  diet  is  free  from  ob- 


Am.  Jour.  Pharm. 
May,  1914. 


The  Vitamines. 


241 


jection  if  it  is  reasonably  varied.  It  is  where  poverty  or  some 
other  compulsion  is  operative  that  nutritional  disasters  are  likely. 

The  condition  of  the  body  in  scurvy  is  quite  different  from 
that  in  beri-beri  and  the  missing  compounds  are  probably  some- 
what unlike.  Some  articles  of  diet  may  protect  against  both ;  some 
may  be  specific  for  only  one.  Allied  with  scurvy  are  the  disorders 
called  ship  beri-beri,  infantile  scurvy  (Barlow's  disease),  and  the 
experimental  scurvies  which  can  be  produced  in  animals  by  limit- 
ing the  intake  to  a  few  foods.  Still  other  pathological  states  may 
be  found  to  have  a  more  or  less  similar  basis.  An  attempt  has 
been  made  to  justify  the  claim  that  pellagra  is  a  deficiency  disease, 
but  this  is  strongly  contested.  Abnormalities  of  early  development 
such  as  rachitis  (rickets)  and,  perhaps,  later  perversions  of  growth 
such  as  cancer  may  be  connected  with  the  lack  of  certain  chemical 
constituents  in  the  income  of  the  body.  '  At  this  point  it  may  be  in 
order  to  say  that  the  diet  itself  may  conceivably  be  ideal  and  yet 
there  may  be  a  failure  to  utilize  the  vitamines  offered  either  because 
of  a  failure  to  absorb  them  or  because  of  the  premature  decomposi- 
tion in  the  alimentary  tract. 

A  few  years  ago  Crichton-Browne,  an  English  authority,  in 
passing  an  unfavorable  judgment  upon  the  dietetic  standards  of 
Chittenden  and  others  called  attention  to  the  fact  that  the  diet 
approved  by  them  seemed  to  correspond  closely  with  that  of  the 
very  poor.  The  comparison  was  based  upon  fuel  value  and  protein 
content.  It  is  now  possible  to  modify  the  statement  that  the  two  are 
precisely  equivalent.  The  low  diet  of  the  New  Haven  school  is  an 
inclusive  one,  while  that  of  the  poor  is  of  limited  variety.  A  supply 
of  the  requisite  minor  bodies — vitamines,  if  we  adopt  the  term — 
is  much  more  surely  to  be  relied  on  in  the  first  case. 

Bunge,  the  Austrian  physiologist,  pointed  out  in  1901  that  sugar 
is  an  unnatural  food,  in  that  it  has  been  refined  to  the  exclusion 
of  all  compounds  but  saccharose.  Foods  which  are  not  deliberately 
prepared  by  industrial  or  domestic  processes  are  always  mixtures, 
however  much  one  constituent  may  predominate.  The  teaching  of 
Sylvester  Graham  in  the  first  half  of  the  nineteenth  century  that 
the  foods  offered  by  nature  should  not  be  separated  into  their  in- 
gredients but  taken  in  their  entirety  is  frequently  reechoed  in  our 
own  day.  In  the  light  of  studies  like  those  of  Funk  it  is  apparent 
that  there  is  a  certain  foundation  for  the  idea  that  foods  may  be 
"  denatured  "  either  by  discarding  valuable  fractions  or  by  modes 


242  Pharmaceutical  Meeting.       ,  {Am,MJa0yuri9uarm- 

of  preparation  which  destroy  essential  compounds.  The  fear  that 
disturbances  of  nutrition  from  such  causes  threaten  the  American 
people  as  a  whole  may  be  dismissed,  but  it  is  interesting  to  have  a 
new  insight  into  a  matter  which  under  certain  conditions  becomes 
of  pressing  importance. 


PHARMACEUTICAL  MEETING. 

At  the  third  Pharmaceutical  Meeting  held  February  20th,  Mr. 
A.  K.  Lobeck  spoke  on  "  A  Roughing  Trip  Across  the  Continent," 
showing  about  150  colored  slides.  While  the  subject  may  have 
seemed  remotely  connected  with  pharmacy,  yet,  as  Mr.  Poley  very 
well  brought  out  in  his  remarks  afterward,  anything  which  will 
attract  the  pharmacist's  attention  to  out-of-door  life  will  be  a  benefit 
to  him  and  tend  to  draw  him  away  from  his  confined  state  of 
existence. 

Mr.  Lobeck  attempted  throughout  the  story  of  the  trip  to  inter- 
pret the  natural  scenery  of  the  country.  The  origin  of  Niagara 
Falls,  the  fact  that  they  are  receding  at  the  rate  of  5  feet  per  year, 
the  geological  reason  for  the  forms  observed  in  the  Garden  of  the 
Gods,  and  the  explanation  of  the  scenery  around  Horse  Shoe 
Curve  were  some  of  the  things  dwelt  upon.  A  summary  of  the 
trip  was  given  showing  in  detail  the  distribution  of  the  expenses  and 
giving  the  average  of  expenses  for  each  day.  Exclusive  of  railroad 
fares  it  was  shown  that  the  average  cost  per  day  was  88  cents,  this 
low  average  being  accounted  for  by  the  fact  that  during  the  trip 
of  63  days,  27  days  were  spent  camping  or  on  ranches,  either  work- 
ing or  under  more  hospitable  circumstances. 


What  is  Sleep?  In  an  article  on  "  Sleep  "  Dr.  Boris  Sidis  says : 
"  Sleep  is  not  a  disease,  not  a  pathological  process  due  to  the  accu- 
mulation of  toxic  products  in  the  brain  or  in  the  system  generally. 
Sleep  is  not  an  abnormal  condition,  it  is  a  normal  state.  Like  the 
waking  states,  sleep  states  are  part  and  parcel  of  the  life-existence 
of  the  individual.  Waking  and  sleeping  are  intimately  related — they 
are  two  different  manifestations  of  one  and  the  same  life-process — 
one  is  as  normal  and  healthy  as  the  other." 


THE  PROCTER  MONUMENT.  PHOTOGRAPH  OF  MODEL  OF  THE  BRONZE 
STATUE,  DESIGNED  BY  EDWARD  BERGE,  AND  TO  BE  ERECTED  IN  WASHING- 
TON, D.  C,  WHEN  COMPLETED. 


THE  AMEBIOAN 


JOURNAL,  OF  PHAEMAC 


Forty  years  have  elapsed  since  the  former  editor  of  this  Journal 
passed  away  on  that  fateful"  night  of  February  10,  1874.  During 
these  forty  years  Pharmacy  has  developed  by  leaps  and  bounds ;  new 
and  weighty  problems  have  arisen  and  have  been  solved,  but  many 
more  remain,  and  the  future  gives  promise  of  still  greater  achieve- 
ments in  the  profession  which  Procter  loved. 

To  John  F.  Hancock,  of  Baltimore,  must  be  given  the  principal 
credit  for  inaugurating  and  carrying  to  successful  fruition  the  work 
of  erecting  a  statue  in  bronze  to  perpetuate  the  memory  of  this  great 
pioneer  in  professional  pharmacy. 

The  ninety-seventh  anniversary  of  his  birthday  was  celebrated 
at  the  Philadelphia  College  of  Pharmacy  on  May  3rd  by  a  special 
meeting  of  his  friends  and  former  students.  Reminiscences  and 
tributes  to  his  memory  were  freely  uttered,  followed  by  a  dinner 
and  a  trip  in  the  afternoon  to  Mount  Holly,  N.  J.,  to  visit  his  summer 
home  and  grave.    Among  those  present  were  the  following: 


JUNE,  1914 


PROFESSOR  WILLIAM  PRO' 


181 7-1874. 
By  Joseph  P.  Remington. 


Dr.  B.  S.  Erwin 
O.  W.  Osterlund 
C.  A.  Weidemann 
Dr.  W.  H.  H.  Githins 
Howard  B.  French 
J.  S.  Beetem 
W.  Estell  Lee 
Thomas  D.  McElhenie 
George  M.  Beringer 
Adolph  W.  Miller 


J.  P.  Remington 
Edward  Berge 
J.  F.  Hancock 
Martin  I.  Wilbert 


C.  B.  Lowe 
C.  H.  La  Wall 


R.  C.  Lippincott 
Otto  Kraus 
Henry  Kraemer 


F.  X.  Moerk 


(243) 


244 


Professor  William  Procter,  Jr. 


Am.  Jour.  Pharm. 
June,  1914. 


Am.  Jour.  Pharm.i 
June,  1914.  f 


Clayton  French  Fellowship. 


245 


Samuel  M.  Bines 
Hugh  Campbell 
Dr.  Henry  A.  Newbold 
Edwin  M.  Boring 


Dr.  F.  E.  Stewart 
E.  B.  Jones 
Harry  P.  Thorn 
Alexander  Dubell 


The  special  object  of  bringing  Procter's  friends  together  was  to 
have  them  comment  upon  and  criticise  a  model  of  a  bronze  statue 
which  it  is  proposed  to  erect  upon  the  grounds  of  the  Smithsonian 
Institution,  at  Washington.  The  sculptor,  Edward  Berge,  has  re- 
produced in  a  remarkable  manner,  from  photographs  and  very  scanty 
material  at  command,  a  model  which  will  serve  as  a  starting  point 
in  the  work  of  moulding  the  bronze  statue. 

The  following  resolution  was  unanimously  passed  by  the  meeting : 
*4  Resolved,  That  the  work  of  Mr.  John  F.  Hancock  in  connec- 
tion with  the  Procter  Memorial  be  approved,  and  that  the  model 
and  design  of  Mr.  Edward  Berge,  of  Baltimore,  for  the  statue  be 
accepted." 

It  is  meet  and  right  to  erect  statues  to  our  honored  dead,  lest 
we  forget,  but  Procter's  greatest  monument  must  ever  be  his  great 
services  to  Pharmacy,  and  especially  his  twenty-eight  years  as 
Editor  of  the  American  Journal  of  Pharmacy. 

"  Could  each  here  vow  to  do  his  little  task  as  the  departed  did  his 
great  one — in  the  manner  of  a  true  man — not  for  a  day,  but  for 
eternity ;  to  live  as  he  counseled,  not  commodiously  in  the  Repu- 
table, the  Plausible,  the  Half ;  but  resolutely  in  the  Whole,  the  Good, 
and  the  True." — Carlyle. 


THE  "CLAYTON  FRENCH  FELLOWSHIP"  IN  THE 
PHILADELPHIA  COLLEGE  OF  PHARMACY. 

When  an  institution  is  well  equipped  especially  for  doing  work 
which  is  not  in  the  regular  routine  of  things  it  seems  a  shame  when 
few  or  none  are  encouraged  to  profit  by  such  favorable  circum- 
stances. Our  institution,  owing  to  its  long  standing,  the  activity  and 
friendly  relations  of  its  faculty  with  the  outside  world,  has  gradually 
accumulated  apparatus  and  materials  which,  owing  to  the  general 
nature  of  things,  can  be  used  only  by  those  who  are  interested  in 
problems  external  to  the  regular  course  of  instruction.  There  is  no 
such  thing,  as  yet,  as  a  post-graduate  course  here,  but  there  has 
recently  been  made  the  first  step  in  that  direction.    The  fellowship 


246 


Clayton  French  Fellowship. 


Am.  Jour.  Phartil. 
June,  1914. 


which  we  are  about  to  mention  will  make  it  possible  for  some 
capable  and  interested  student  to  pursue  work  along  .some  particular 
line  of  investigation  which  would  otherwise  go  untouched  but  for 
this  stimulus.  Both  the  student  and  the  college  will  profit  thereby, 
and  there  is  also  the  chance  that  it  may  lead  to  some  big  benefit  to 
the  profession  of  pharmacy  as  a  science.  It  is  a  hard  enough  thing 
to  settle  down  to  the  prosaic  task  of  fathoming  out  a  difficult  prob- 
lem, and  anything  like  this  which  makes  it  an  honor  and  which  re- 
duces also  the  financial  burden  of  such  a  task  is  almost  essential  to 
the  building  up  of  a  great  work. 

In  order  to  provide  for  fellowships,  and  that  those  who  would 
contribute  to  such  endowments  might  know  to  what  purposes  they 
would  be  applied,  a  new  article  on  Scholarships  and  Fellowships 
has  been  incorporated  into  the  By-laws  of  the  Philadelphia  College 
of  Pharmacy.   This  article  reads  as  follows : 

"  Scholarships  and  Fellowships  covering  instruction  given  in  the 
College  or  studies  pursued  elsewhere  by  direction  of  its  Board  of 
Trustees,  may  be  established  by  the  Board  of  Trustees  as  funds  for 
such  purposes  are  provided. 

"  To  found  a  Pharmacy  Course  Scholarship,  a  sum  of  not  less 
than  $3000  shall  be  paid  to  the  College.  The  student  to  whom  such 
scholarship  is  awarded  shall  receive  free  instruction  in  all  of  the 
lectures  and  laboratories  in  the  course  leading  up  to  a  degree  in 
Pharmacy  for  the  period  for  which  the  award  is  made. 

"  To  found  a  Special  Scholarship  or  a  Partial  Pharmacy  Course 
Scholarship,  a  sum  of  not  less  than  $1500  shall  be  paid  to  the  Col- 
lege. In  no  case  shall  the  sum  paid  be  less  than,  when  invested,  will 
produce  an  income  equivalent  to  the  fees  required  by  the  College 
from  students  for  similar  instruction.  The  donor  may  designate 
the  course  of  lectures  or  laboratory  instruction  to  which  such  special 
bequest  or  donation  is  to  be  applied.  The  student  to  whom  such 
Special  Scholarship  or  Partial  Pharmacy  Course  Scholarship  is 
awarded  shall  receive  free  instruction  in  the  lectures  and  laboratories 
named  for  the  period  for  which  the  award  is  made. 

"  To  found  a  Research  Fellowship,  a  sum  of  not  less  than  $5000 
shall  be  paid  to  the  College ;  the  income  from  such  a  foundation  is  to 
be  paid  to  the  student  to  whom  such  fellowship  is  awarded  to  pay  for 
the  tuition,  materials,  and  apparatus  used  in  the  research  work  and 
as  compensation  for  such  aid  in  the  laboratories,  museums,  library, 
or  other  department  of  the  College  as  the  recipient  may  render. 


Am.  Jour.  Pharm. 
June,  1914. 


Clayton  French  Fellowship. 


247 


"  The  founder  of  a  fellowship  may  designate  the  title  of  the 
fellowship  and  the  special  investigation,  science,  or  department  to 
which  the  research  is  to  be  directed,  and  may  select,  from  time  to 
time,  the  fellow  to  whom  the  fellowship  is  to  be  awarded.  In  the 
absence  of  such  designation  or  selection  the  Board  of  Trustees  shall 
decide  the  title  and  the  application  of  the  research,  and,  subject  to 
confirmation  by  the  Board  of  Trustees,  nominate  from  time  to  time 
the  fellow  on  written  application  setting  forth  the  subject  of  re- 
search work  that  is  to  be  engaged  in,  preference  is  to  be  given  to 
post-graduate  study  in  the  sciences  associated  with  pharmacy. 

"  If  any  student  to  whom  a  scholarship  or  a  fellowship  is  awarded 
is  found  to  be  of  improper  character,  or  is  deficient  in  mentality  or 
scholarship,  or  fails  to  attend  the  instruction  or  to  pass  satisfactory 
examinations,  the  award  shall  be  cancelled. 

"  A  scholarship  or  a  fellowship  is  awarded,  in  accordance  with  the 
By-Laws  and  Rules  and  Regulations  established  by  the  Board  of 
Trustees,  to  the  student  named  and  for  the  period  specified  and  can- 
not be  transferred  by  the  recipient. 

"  All  moneys  received  by  the  College  for  the  purpose  of  founding 
a  scholarship  or  fellowship  shall  be  invested  by  the  Finance  Com- 
mittee in  accordance  with  their  best  judgment,  and  a  separate 
account  shall  be  kept  of  each  such  scholarship  or  fellowship. 

"  If  any  donation  or  bequest  received  for  the  purpose  of  founding 
a  scholarship  be  insufficient  for  the  purpose  intended,  then  such  sum 
received  shall  be  invested  by  the  Finance  Committee,  and  when  the 
aggregate  of  the  principal  and  accrued  interest  is  sufficient  for  the 
purpose  intended,  the  scholarship  shall  be  established  by  the  Board  of 
Trustees. 

"  The  Board  of  Trustees  shall  have  authority  to  offer,  in  the 
name  of  the  College,  free  scholarships  to  students  of  such  public 
schools  or  other  educational  institutions  as  the  Board  may  designate." 

At  a  recent  meeting  of  the  Board  of  Trustees  President  French 
announced  that  Mrs.  Mary  French  Banks,  of  Philadelphia,  had 
donated  through  him  the  sum  of  $5000  for  the  establishment  of  a 
fellowship  as  a  memorial  to  her  father,  Clayton  French.  The  Board 
gratefully  accepted  the  sum  and  established  a  fellowship,  to  be 
known  as  the  "  Clayton  French  Fellowship."  The  -following  is  a 
copy  of  the  letter  of  transmittal  to  Mrs.  Banks  by  the  Chairman  of 
the  Board  of  Trustees: 


248 


Clayton  French  Fellowship. 


{ 


Am.  Jour.  Pliarui. 
June,  1914. 


May  5,  1914. 


Mrs.  G.  W.  Banks, 
Philadelphia,  Pa. 

Dear  Madam: 

Mr.  Howard  B.  French,  at  the  meeting  of  the  Board  of  Trustees 
of  the  Philadelphia  College  of  Pharmacy  this  p.m.,  presented  your 
check  drawn  to  his  order  and  endorsed  by  him  to  the  Treasurer  of 
the  College  for  $5000  to  establish  a  Fellowship  as  a  memorial  to 
your  deceased  father,  Clayton  French.  Permit  me  to  assure  you 
the  appreciation  of  the  Board  for  the  courtesy  you  have  extended 
and  the  honor  that  you  bestow  upon  one  who  many  years  ago  was 
a  student  in  this  institution. 

The  following  resolutions  were  unanimously  passed  and  ordered 
to  be  forwarded  to  you : 

"  Resolved,  That  the  Board  of  Trustees  of  the  Philadelphia  Col- 
lege of  Pharmacy  gratefully  acknowledge  receipt  of  Five  Thousand 
Dollars  ($5000),  through  the  hands  of  Mr.  Howard  B.  French,  from 
Mrs.  Mary  F.  Banks,  to  be  used  in  establishing  a  Fellowship  in  honor 
of  her  deceased  father,  the  late  Clayton  French. 

"  Resolved,  That  a  marble  tablet  be  erected  in  the  hallway  of 
the  College,  bearing  the  following  inscription : 


"  Resolved,  That  the  Five  Thousand  Dollars  ($5000)  donated 
for  establishing  the  Clayton  French  Fellowship  shall  be  invested  in 
our  mortgage  account,  and  that  the  income  therefrom  shall  be  used 
for  advanced  research  work." 

Assuring  you  the  deepest  appreciation  of  the  Board,  I  have  the 
honor  to  be 


1824 


1890 


Clayton  French 


FELLOWSHIP 


Established  by  his  daughter 
Mary  French  Banks 
May  16th,  1914 


Yours  truly, 


George  M.  Beringer, 
Chairman  of  the  Board. 


Am'jirer'i9ihrm'}   Volumetric  Estimation  of  Sulphates.  249 


THE  VOLUMETRIC  ESTIMATION  OF  SULPHATES. 
By  Horace  North. 

Although  S04  is  easily  the  most  important  acidic  ion  concerned 
in  the  operations  of  industrial  chemistry,  there  is  at  the  present  time 
no  satisfactory  method  of  general  application  for  its  volumetric 
estimation.  A  method  is  proposed  which,  in  the  light  of  numerous 
experiments,  promises  to  be  widely  useful.  Subject  to  certain  limita- 
tions which  will  be  considered  in  due  course,  the  method  is  applicable 
in  the  presence  of  the  ions  Li,  Na,  K,  NH4,  Cu  -,  Mg,  Ca,  Sr,  Zn, 
Cd,  Hg-,  Al,  Ni,  Co,  CI,  P04,  B407.  All  data  are  referred  to  one 
standard  solution  which  is  readily  prepared  of  exact  strength  and 
which  is  permanent.  The  end  point  of  the  titration  is  clearly  defined. 
When  all  is  in  readiness  an  estimation  requires  fifty  minutes. 

In  1877  Hinman  1  proposed  to  determine  sulphuric  acid  as  fol- 
lows:  To  a  slightly  acid  solution  of  a  sulphate  heated  to  boiling 
is  added  a  small  excess  of  a  solution  of  barium  chromate  in  hydro- 
chloric acid,  barium  sulphate  is  precipitated,  then  the  solution  is 
neutralized  with  ammonia  which  precipitates  the  remaining  barium 
chromate,  the  precipitates  of  barium  sulphate  and  chromate  are 
filtered  off,  and  the  chromic  acid,  determined  in  the  filtrate  by 
means  of  stannous  chloride,  is  equivalent  to  the  sulphuric  acid  in 
the  original  solution. 

This  method  is  limited  in  its  application ;  in  particular,  metals 
forming  chromates  insoluble  in  the  presence  of  ammonia  as  well  as 
phosphates  and  borates  interfere.  Various  modifications  2  designed 
to  correct  its  inherent  defects  have  been  suggested  without,  however, 

1  Amer.  Journ.  Science  and  Arts,  114,  478. 

2  Andrews,  Am.  Chem.  Journ.,  2,  567;  32,  476-480. 

Marboutin  and  Molinie,  Bull.  Soc.  Chim.,  17,  950-955  ;  19,  713-717.  Journ. 
Soc.  Chem.  Ind.  (1897),  1041;  (1898)  874. 
Reuter,  Chem.  Ztg.  (1898),  357. 
Telle,  /.  Pharm.  Chim.,  7,  165-170. 
Bruhns,  Z.  anal.  Chem.  (1906),  573. 
Komarowsky,  Chem.  Zcit.,  32,  770. 
Mitchell  and  Smith,  Chem.  Soc.  Proc,  25,  291. 
Repiton,  Monit:  Sclent.,  24,  382-384. 

Holliger,  Stahl  u.  Eiscn,  30,  1376-1378;  Z.  Anal.  Chem.,  49,  84-93; 
angew.  Chem.,  22,  436-449. 

Roemer,  Z.  Anal.  Chem.,  49,  490-492. 


250  Volumetric  Estimation  of  Sulphates.   { Am-j^J; 

extending  its  usefulness.  Thus,  it  having  been  shown  that  HC1  is 
oxidized  on  prolonged  contact  with  Cr207,  the  strength  of  the  stand- 
ard solution  being  thereby  altered,  trichloracetic  acid  was  proposed 
to  hold  the  BaCr04  in  solution.  In  any  case  it  is  impossible  to  pre- 
cipitate BaS04  in  the  presence  of  chromate  without  coprecipitation 
of  the  latter  in  some  degree.  For  this  reason  and  in  order,  further, 
to  avoid  the  uncertainty  arising  from  the  instability  of  solutions  of 
barium  chromate,  some  authors  recommend  separate  solutions  of 
barium  and  chromate,  the,  BaS04  being  precipitated  before  the  in- 
troduction of  the  chromate.  Another  way  of  avoiding  the  instability 
of  acid  solutions  of  barium  chromate  is  to  employ  a  mechanical 
suspension  or  cream  of  the  salt.  This  idea  would  not  seem  to  be  in 
accord  with  good  volumetric  practice.  Calcium  carbonate  has  been 
used  in  place  of  ammonia,  though  with  no  very  obvious  advantages. 
Various  means  have  been  adopted  for  the  estimation  of  the  Cr207. 

The  volumetric  solutions  required  in  the  proposed  method  are : 

Normal  Potassium  Bichromate. — Dissolve  49.033  gms.3 
K2Cr207,  previously  powdered  and  dried  at  1200  C,  in  sufficient 
water  to  measure  1000  c.c. 

The  solution  is  normal  with  respect  to  oxidizing  power. 

Tenth-normal  Sodium  Thiosulphate. — Measure  10  c.c.  n/i 
KXr,C)7  into  a  100  c.c.  glass-stoppered  volumetric  flask  and  make 
up  to  the  mark.  Measure  20  c.c.  of  this  solution  into  a  500  c.c. 
Florence  flask  containing  1  gm.  KI  just  previously  dissolved  in 
20  c.c.  dilute  sulphuric  acid  (100  c.c.  cone.  H2S04  +  900  c.c.  water), 
rinse  down  the  sides  of  the  flask  with  60  c.c.  water,  mix  the  liquids, 
cover  the  flask  with  a  watch-glass  and  let  stand  six  minutes.  Dilute 
the  liquid  with  150  c.c.  water  and  titrate  the  free  I  with  a  solution 
of  sodium  thiosulphate  (25  gms.  Na2S203  +  5H20  in  1000  c.c), 
adding  starch  indicator  near  the  end.  Divide  20,000  by  the  number 
of  c.c.  required  and  dilute  each  litre  of  the  Na2S203  solution  to  the 
volume  indicated. 

The  above  is  essentially  the  method  of  Seubert  and  Henke  4  for 
the  iodometric  estimation  of  Cr207. 

Third-normal  Barium  Chloride. — The  solution  is  equivalent  to 
the  dichromate  solution  and  contains  40.72  gms.  BaCL  +  2FLO  per 
litre. 


3  The  international  atomic  weights  for  1913  were  used  throughout  the 
investigation. 

4  Zeit.  f.  ang.  C,  1900,  1147;  "  Volumetric  Analysis,"  Sutton,  1904,  184. 


Am*  /me,'  i9i4.rm' }   Volumetric  Estimation  of  Sulphates.  251 

Measure  4  c.c.  HQ  (sp.  gr.  1.12),  40  c.c.  water  and  10  c.c. 
barium  chloride  solution  (about  43  gms.  BaCL  +  2HLO  in  1000  c.c.) 
into  a  100  c.c.  glass-stoppered  volumetric  flask,  heat  the  liquid  to 
boiling,  run  in  10  c.c.  n/i  K2Cr207,  rinse  down  the  neck  of  the 
flask  with  10  c.c.  water  and  without  further  heating  add  drop  by 
drop  with  constant  shaking  a  mixture  of  15  c.c.  ammonia  water  (sp. 
gr.  0.98)  and  2  c.c.  36  per  cent,  acetic  acid.  Cool  the  mixture  to  the 
normal  temperature,  make  up  to  the  mark  and  filter  with  the  aid  of 
suction  through  an  asbestos  felt  previously  formed  in  the  usual  man- 
ner, then  dried  at  about  no°  C.  Titrate  40  c.c.  of  the  filtrate  under 
the  conditions  specified  in  the  standardization  of  the  n/io  Na2S203, 
except  that  40  c.c.  water  are  used  in  place  of  60  c.c,  the  total  volume 
of  the  solution  during  the  six-minute  period  of  standing  being 
100  c.c.  Divide  20,000  by  the  number  of  c.c.  n/io  Na2S2Oa  re- 
quired, and  dilute  each  litre  of  the  BaCL  solution  to  the  volume  in- 
dicated. A  new  trial  is  then  to  be  made  with,  if  necessary,  the 
slight  readjustment  required. 

An  estimation  of  S04  is  carried  out  as  follows : 

Transfer  the  sulphate  solution  containing  about  0.16  gm.  S04  to 
a  100  c.c.  glass-stoppered  volumetric  flask,  dilute  to  a  volume  of 
30  c.c,  add  sufficient  HC1  (sp.  gr.  1.12)  so  that  the  total  amount, 
present  is  4  c.c  (if  acidity  is  unknown,  first  neutralize  with  am- 
monia), heat  the  liquid  to  boiling,  run  in  20  c.c  N/3  BaCl2,  again 
heat  to  boiling,  run  in  10  c.c.  n/i  K2Cr207,  rinse  down  the  neck  of 
the  flask  with  10  c.c.  water  and  without  further  heating  add  drop 
by  drop  with  constant  shaking  a  mixture  of  15  c.c  ammonia  water 
(sp.  gr.  0.98)  and  2  c.c.  36  per  cent,  acetic  acid.  Complete  the 
experiment  as  specified  under  the  standardization  of  the  N/3  BaCl2. 

C.c.  n/io  Na2S203  required  X 0.008  =  gm.  S04  originally  taken. 

The  reaction  between  equivalent  solutions  of  K2Cr207  and 
BaCL  is  -expressed  by  the  equation :  K2Cr207  +  BaCL  +  H20  = 
BaCr04  +  K2Cr04  +  2HCI.  The  resulting  HC1  retains  in  solu- 
tion a  considerable  portion  of  the  Ba.  On  neutralizing  with  am- 
monia all  of  the  Ba  is  thrown  out  as  chromate  and  half  the  Cr 
originally  taken  remains  in  solution. 

A  large  number  of  preliminary  experiments,  the  details  of  which 
it  is  hardly  necessary  to  give,  demonstrated  the  following  points : 

(1)  When  cold  solutions  of  K2Cr2Q7  and  BaCL  are  mixed  and 
neutralized,  the  precipitate  of  BaCrQ4  carries  down  soluble  chro- 
mate in  considerable  and  variable  amounts. 


252  Volumetric  Estimation  of  Sulphates.  {Am'jun7i9urm' 

(2)  The  same  error  in  less  degree  occurs  when  the  BaCl2  solu- 
tion is  added  to  the  diluted  and  boiling  K2Cr207  solution  and  the 
neutralization  effected  at  the  boiling  point. 

(3)  The  error  is  eliminated  only  when  the  K2Cr207  and  BaCl2 
solutions  are  mixed  in  the  presence  of  sufficient  HQ  to  prevent  the 
precipitation  of  BaCr04,  and  then  ammonia  water  is  added  drop 
by  drop  to  the  hot  liquid ;  further,  the  ammonia  water  must  be  fairly 
dilute  so  that  not  too  much  BaCr04  is  thrown  out  at  once  as  the 
liquid  approaches  neutrality. 

Acetic  acid  is  unaffected  by  dichromate  under  the  conditions  of 
the  procedure.  10  c.c.  n/i  K2Cr207  were  measured  into  a  100  c.c, 
volumetric  flask,  40  c.c.  water  and  1  c.c.  36  per  cent,  acetic  acid 
were  added,  the  liquid  was  boiled  1  minute,  cooled  and  made  up  to 
the  mark.  20  c.c.  required  19.95  c.c.  n/io  Na2S203.  An  inde- 
pendent experiment  done  in  the  same  manner  required  20  c.c.  n/io 
Na2S203. 

The  use  of  acetic  acid  widens  the  application  of  the  method 
greatly.  Numerous  chromates  insoluble  in  the  presence  of  am- 
monia readily  dissolve  in  acetic  acid.  The  latter  also  permits  of  the 
application  of  the  method  in  the  presence  of  borates  and,  especially, 
of  phosphates  in  limited  amounts.  It  is  highly  important  that  the 
excess  of  acetic  acid  be  not  much  greater  than  0.5  c.c,  which  is  nearly 
equivalent  to  10  c.c.  n/i  K2Cr207.  An  undue  excess  would  exert 
a  marked  influence  on  the  solubility  of  the  BaCr04  .and  lead  to  too 
high  results.5  The  quantities  of  reagents  specified  are  such  that 
under  the  actual  working  conditions  of  the  procedure  the  excess  of 
acetic  acid  finally  present  is  close  to  0.5  c.c. 

The  method  being  designed  for  technical  use,  the  volumes  re- 
quired to  be  handled  are  kept  within  moderate  limits. 

In  the  volumetric  standardization  of  the  BaCL  under  the  con- 
ditions specified  various  errors  compensate  each  other  so  perfectly 
that  gravimetric  assays  show  very  nearly  theoretical  results.  Ob- 
viously this  fact  is  of  the  highest  importance  in  the  practical  opera- 
tion of  the  method.  If  this  were  not  so  it  would  be  necessary  to 
standardize  the  BaCL  gravimetrically  and  apply  a  correction  to  the 
titration.  In  the  course  of  the  work  two  independent  sets  of  reagents 
were  prepared.   First  lot  of  BaCL  :  10  c.c.  yielded  0.3885  gm.  BaS04, 

5  Cf.  Bray,  "  A  System  of  Qualitative  Analysis  for  the  Common  Ele- 
ments," /.  Am.  Ch.  Soc,  1909,  611-637. 


Amjune,r'i9Pi4arm'}   Volumetric  Estimation  of  Sulphates.  25$ 

equivalent  to  0.4066  gm.  BaCL  +  2H20.  Second  lot  of  BaCl2 : 
10  c.c.  yielded  0.3886  gm.  BaS04,  equivalent  to  0.4067  gm.  BaCL 
+  2H20.  Theory  demanded  0.4072  gm.  BaCL,  +  2H2Q.  Error 
=  0.1  per  cent. 

Ordinarily  about  0.16  gm.  S04  should  be  taken.  If,  however, 
the  proportion  of  SC4  is  so  small  that  0.16  gm.  cannot  be  taken 
without  increasing  unduly  the  concentration  of  the  other  ions,  it  is 
necessary  to  take  into  account  the  error  arising  from  the  solubility 
of  the  BaCr04,  which,  under  the  conditions,  is  represented  by  0.3  c.c. 
n/io  Na2S203  per  40  c.c.  of  the  filtrate.  For  example,  10  gms. 
table  salt  were  dissolved  in  sufficient  water  to  measure  100  c.c. 
Volumetric  and  gravimetric  estimations  were  made  on  10  c.c. 
portions.  40  c.c.  of  the  filtrate  required  1.1  c.c.  n/io  Na2S20;r  The 
correction  having  been  deducted,  0.0064  gm.  S04  was  indicated. 
BaS04  found:  0.0152  gm.,  equivalent  to  0.0062  gm.  S04. 

Table  I  presents  a  large  part  of  the  experimental  data  and  is  self- 
explanatory. 

Notes  Supplementary  to  Table  I. 

a.  Carefully  recrystallized  and  dehydrated  by  gentle  ignition;  purity  also 
established  gravimetrically  in  the  course  of  some  previous  work. 

.  b.  Cu-  does  not  interfere,  provided  care  is  taken  to  prevent  the  premature 
formation  of  cuprous  salt.  Should  this  occur,  the  titrating  fluid  becomes 
cloudy.  Shaking  and  standing  may  clear  it.  The  n/io  Na^S-Oa  should  be 
added  in  small  portions  with  vigorous  shaking.  The  first  disappearance  of 
the  blue  color  is  taken  as  the  end.  The  titration  may  also  be  carried  out 
without  starch  indicator,  the  thiosulphate  being  run  in  until  there  is  no  further 
change  in  color  and  the  liquid  acquires  a  slight  permanent  opalescence. 

c.  Mg  occasions  a  positive  error  variable  between  1  and  2  per  cent.  The 
substitution  of  caustic  soda  for  ammonia  does  not  reduce  this  error. 

d.  Two  independent  experiments. 

e.  Although  SrCrCXt  is  readily  soluble  under  the  conditions  of  the  pro- 
cedure, the  slight  solubility  of  SrSOi  greatly  limits  the  application  of  the 
method  in  the  presence  of  Sr. 

/.  Less  the  correction  0.3  =  2  c.c. 

g.  The  salt  was  badly  effloresced. 

h.  The  study  of  this  element  led  to  the  addition  of  the  ammonia  and 
acetic  acid  mixed.  Alumina  once  precipitated  by  ammonia  redissolves  with 
great  difficulty  in  so  weak  an  acid  as  acetic.  Further,  precipitated  alumina 
occludes  soluble  chromate.  Under  the  conditions  of  the  procedure  the 
aluminium  remains  in  solution  or,  at  most,  the  liquid  becomes  slightly 
opalescent. 

i.  The  usual  formula  with  7H2O  was  assumed;  hence  the  weight  taken. 
The  salt  actually  contained  6H2O. 


Volumetric  Estimation  of  Sulphates.  {^jS^iSS^ 


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Ata:i,meri9Harm'}   Volumetric  Estimation  of  Sulphates.  2$$ 

Phosphates.— 0.5  gm.  NaJiPQ4 +12ILO,  4  c.c.  HQ  (sp.  gr. 
1. 1 2),  40  c.c.  water  and  10  c.c.  N/3  BaCL,  were  mixed  in  a  100  c.c. 
flask,  the  liquid  was  heated  to  boiling,  20  c.c.  water  were  added,  then 
drop  by  drop  with  constant  shaking  a  mixture  of  15  c.c.  ammonia 
water  (sp.  gr.  0.98)  and  2  c.c.  36  per  cent,  acetic  acid  was  added. 
Near  the  end  a  considerable  amount  of  precipitate  appeared  which 
failed  to  redissolve  on  shaking  or  boiling.  There  was  much  phos- 
phate still  in  solution.  Various  other  amounts  of  phosphate  were 
tried  under  the  same  conditions.    The  results  are  given  in  Table  II. 

Blank  0  tests  were  done  in  the  presence  of  various  amounts  of 
phosphate.    The  results  are  given  in  Table  III. 


Table  II. 


Na2HP04+  12H2O  taken 

Precipitate 

0.5  gm  

Considerable. 

0.3  gm  

Small. 

0.25  gm  

Slight. 

0.2  gm  

Slight.  .. 

0.15  gm  

Barely  visible. 

0.1  gm  

None. 

Blank  tests  were  done  in  the  presence  of  HgCL  (0.45  gm. )  and 
Na2B407  +  10  HaO  (0.5  gm.),  respectively.  Neither  substance 
interfered. 

Table  III. 


Na2HP04  +  i2H20  taken 

N/io  Na2S2°3  required 

Per  cent,  error 

0.5  gm. 

21.3  C.C. 

+  6.5 

0.3  gm. 

20.6  C.C. 

>  +3- 

0.25  gm. 

20.3  c.c. 

+  1.5 

0.2  gm. 

20.3  c.c. 

+  1-5 

0.15  gm. 

20.05  c'c- 

+0.25 

0.1  gm. 

20  C.C. 

0 

Iron. — Fe-  is,  of  course,  inadmissible.  Fe  -,  if  present  in  the 
final  titration,  liberates  I  from  KI  and  vitiates  the  result.  Fe  -  • 
may  be  completely  removed  from  the  solution  as  basic  ferric  acetate 
by  boiling  the  liquid  after  adding  the  mixture  of  ammonia  and 
acetic   acid.    Unfortunately  coprecipitation  of   soluble  chromate 


8  By  blank  test  is  to  be  understood  a  test  in  which  equal  volumes  of  the 
KjO^Ot  and  BaCb  solutions  are  taken,  as  in  the  standardization  of  the  BaCb. 


256  The  Patent  Medicine  Problem.       (Am  Jour  pim™. 

^  \      June,  1914. 

occurs.  The  error  is  therefore  negative  and  is  too  considerable  to 
be  neglected  even  in  rough  work.  For  example,  the  error  in  an 
experiment  on  ferric  alum  [FeNH4(S04)2  +  12FLO]  amounted  to 
—  8  per  cent. 

Chromium, — A  large  number  of  experiments  was  done  on 
chrome  alum.  The  results  were  much  too  high  and  very  erratic. 
Indications  pointed  to  the  formation  of  chromous  salts. 

Analytical  Department,  Lehn  &  Fink,  New  York. 


THE  PATENT  MEDICINE  PROBLEM.1 
By  M.  I.  Wilbert,  Washington,  D.  C.  . 

The  patent  medicine  problem,  as  it  presents  itself  to  American 
pharmacists  to-day,  is  neither  novel  nor  popular,  and  its  continued 
growth  has  long  since  been  recognized  as  a  menace  to>  the  devel- 
opment of  pharmacy  as  a  .desirable  occupation.  The  business  itself 
has  developed  as  the  joint  off  spring  of  cupidity  and  credulity  and  1 
from  a  very  early  period  has  been  the  one  object  regarding  which 
members  of  the  various  branches  of  the  drug  trade  have  differed 
on  more  frequently  and  more  widely  than  on  any  other. 

While  it  is  generally  recognized  that  the  manufacture,  sale  and 
use  of  so-called  patent  medicines  should  be  considered  primarily 
as  a  public  health  problem,  the  business  from  the  drug  trade  point 
of  view  also  involves  economic  questions  which  cannot  well  be 
ignored  and  which  have,  at  times  at  least,  quite  overshadowed  all 
public  health  considerations.  That  the  economic  feature  of  the 
problem  is  on  the  increase  rather  than  decrease  is  evidenced  by  an 
editorial  in  the  National  Druggist  (1912,  v.  42,  p.  414)  which  asserts 
that  the  number  of  establishments  engaged  in  the  manufacture  of 
patent  and  proprietary  medicines  in  1899  was  2>r54>  and  in  1909 
was  3,642.  The  value  of  the  products  at  the  factories  in  1899  was 
$88,791,000,  and  in  1909  was  $141,942,000,  an  increase  of  approxi- 
mately 70  per  cent,  in  ten  years. 

Whether  the  public  health  or  the  economic  side  of  the  problem 
is  to  be  given  the  preference  in  the  near  future  is  a  question  that  is 
well  worth  considering,  and  one  which  by  the  recent  action  of  the 


1  Presented  at  a  meeting  of  the  City  of  Washington  branch  of  the  Amer- 
ican Pharmaceutical  Association,  February  18,  1914. 


Am'junri9ih4arm'}       The  Patent  Medicine  Problem.  257 

American  Pharmaceutical  Association  is  once  more  set  squarely 
before  the  American  pharmacists  for  reply  or  action. 

The  patent  medicine  problem  as  it  is  now  before  the  members  of 
the  American  Pharmaceutical  Association  for  discussion,  was  out- 
lined in  an  editorial  by  the  general  secretary  of  the  Association,  in 
the  Journal  for  April,  1913  (pp.  425-428).  This  editorial  points  out 
that  the  duty  of  the  pharmacist  to  himself  and  to  the  public,  in 
connection  with  patent  medicines,  is  to  define  if  possible  the  legiti- 
mate status  for  remedies  of  this  kind,  and  to  differentiate  between 
acceptable  and  non-acceptable  preparations. 

This  proposition  was  presented  to  the  Council  of  the  American 
Pharmaceutical  Association  at  the  Nashville  meeting,  and  after 
considerable  discussion  it  was  agreed  to>  appoint  a  Commission  on 
Proprietary  Remedies  to  consider  the  following  general  propositions : 

"  1.  To  inquire  into  and  report  to  the  Council  from  time  to  time 
upon  the  general  subject  of  proprietary  medicines,  in  their  relations 
to  pharmacy,  medicine  and  the  public  health. 

"  2.  To  inquire  whether  any  of  the  proprietary  medicines,  com- 
monly -known  as  patent  medicines,  contain  alcohol  or  narcotic  drugs 
in  sufficient  amount  to  render  them  liable  to  create  a  drug  habit,  or 
to  satisfy  such  habits  where  otherwise  created. 

"3.  To  inquire  whether,  or  to  what  extent,  the  commonly  adver- 
tised patent  medicines  contain  potent  drugs  in  sufficient  amount  to 
render  them  dangerous  in  the  hands  of  the  laity. 

"  4.  To  inquire  into  the  extent  to  which  ^patent  medicines  are 
fraudulently  advertised,  or  differ  in  properties  or  origin  from  the 
claims  made  for  them,  and  the  extent  to  which  they  are  advertised 
for  the  cure  of  diseases  generally  recognized  by  the  medical  science 
as  at  present  being  incurable."  (7.  Am,  Pharm.  Assoc.,  1913,  v.  2, 
p.  1195.) 

As  the  Commission  has,  so  far  as  known,  made  no  report  to  the 
Council  of  the  American  Pharmaceutical  Association,  there  is,  as 
yet,  no  indication  as  to  what  will  or  will  not  be  the  attitude  of  this 
Commission  toward  the  preparations  now  on  the  market  or  to  be 
marketed  in  the  future.  Some  idea  of  the  stand  that  must  be  taken 
by  the  members  of  the  Commission  if  they  desire  to>  make  for 
progress  rather  than  retrogression  is  evidenced  by  what  has  already 
been  accomplished,  not  alone  by  the  American  Pharmaceutical  Asso- 
ciation, but  also  by  other  related  organizations,  particularly  the 
American  Medical  Association. 


258  The  Patent  Medicine  Problem.        { Am;Tlmer"i9ih4arm' 

Not  to  go  too  extensively  into  the  history  of  the  agitation  re- 
lating to  the  manufacture  and  sale  of  patent  medicines,  more  popu- 
larly designated  as  nostrums,  we  may  well  confine  ourselves  to  the 
published  records  of  the  two  national  associations  directly  interested : 
the  American  Pharmaceutical  Association  and  the  American  Medical 
Association,  both  organized  somewhat  over  sixty  years  ago. 

The  American  Medical  Association  almost  annually,  from  the 
time  of  its  preliminary  meeting  in  the  city  of  New  York,  in  1846,  to 
its  reorganization  at  Saratoga  Springs  in  1902,  adopted  resolutions 
condemning  nostrums  and  secret  remedies  of  all  kinds,  and  pointed 
out  objectionable  features  connected  with  them.  Previous  to*  the 
reorganization  of  the  Association  on  the  present  basis,  however, 
little  or  nothing  of  practical  value  was  accomplished. 

The  American  Pharmaceutical  Association  has  also  devoted  con- 
siderable time  and  space  to  the  discussion  of  problems  connected 
with  the  manufacture  and  sale  of  patent  and  proprietary  remedies. 
A  cursory  review  of  the  proceedings  of  the  Association  suggests  the 
rather  interesting  fact  that  this  agitation  appears  to  have  developed 
in  cycles  and  to  have  been  markedly  acute  in  decennial  waves,  the 
maximum  height  of  the  agitation  being  evidenced  in  the  early  years 
of  the  decennium.  Thus,  beginning  with  the  Proceedings  for  1853, 
the  second  meeting  of  the  Association,  we  find  the  following  reso- 
lution, which  was,  on  motion  of  Joseph  Laidley,  substituted  for  one 
previously  offered  by  C.  B.  Guthrie,  and  adopted  by  a  majority  of 
the  members  present! 

"  Resolved,  That  the  American  Pharmaceutical  Association  be- 
lieves that  the  use  and  sale  of  secret  or  quack  medicines  is  wrong  in 
principle  and  is  in  practice  attended  with  injurious  effects  to  both 
the  profession  and  the  public  at  large,  and  believes  it  to  be  the  duty 
of  every  conscientious  druggist  to  discourage  their  use. 

"  Resolved,  That  this  Association  earnestly  recommend  to  our 
pharmaceutical  brethren  to  discourage  by  every  honorable  means 
the  use  of  these  nostrums ;  to  refrain  from  recommending  them  to 
their  customers ;  not  to  use  any  means  of  bringing  them  into  public 
notice ;  not  to  manufacture  or  to  have  manufactured  any  medicine, 
the  composition  of  which  is  not  made  public;  and  to  use  every 
opportunity  of  exposing  the  evils  attending  their  use,  and  the  false 
means  which  are  employed  to  induce  their  consumption."  {Proc. 
Am.  Pharm.  Assoc.,  1853,  p.  17.) 


Am.  Jour.  Pharm.  i       jne  Patent  Medicine  Problem.  259 

June,  1914.  J 

The  agitation  in  the  next  decennium  was  largely  centered  about 
the  manufacture  of  fluid  extracts  and  the  development  of  proprie- 
tary rights  in  preparations  of  this  type,  and  ten  years  later  we  find 
a  similar  line  of  activity  developing  in  connection  with  elixirs,  which 
at  that  time  were  so  popular.  At  the  end  of  another  decennium, 
however,  the  attention  of  members  of  the  Association  was  again 
directed  to  patent  medicines  of  the  nostrum  type  by  a  resolution 
offered  by  Prof.  A.  B.  Prescott,  of  Ann  Arbor,  to  the  effect  that  a 
committee  of  three  members  be  appointed  to  agree  upon  the  most 
feasible  and  suitable  legislation  to  secure  a  sufficient  statement  of 
the  composition  of  proprietary  medicines,  on  the  package  of  the 
same,  and  the  more  feasible  and  efficient  action  to  be  taken  by  the 
Association  in  regard  to  the  matter.  The  committee  appointed  con- 
sisted of  Albert  B.  Prescott,  Frederick  Hoffmann  and  Charles  Rice. 
This  committee,  at  the  succeeding  meeting  of  the  Association,  pre- 
sented a  lengthy  report  on  the  nature  of  desirable  legislation  regard- 
ing the  manufacture  and  sale  of  proprietary  remedies,  and  also  a 
draft  of  an  act  regulating  the  sale  of  proprietary  medicines.  The 
committee  in  its  report  offered  a  resolution  which  was  subsequently 
adopted  by  the  members  of  the  Association  present,  to  the  effect 
"  that  it  is  the  deliberate  opinion  of  this  Association  that  the  labels 
of  proprietary  medicines  ought  to'  carry  a  statement  of  their  con- 
stituents." {Proc.  Am.  Pharm.  Assoc.,  1885,  v.  33,  pp.  394-398.) 
As  evidence  of  the  need  for  action  along  these  lines  the  committee 
said  in  part: 

"  All  medicines,  and  articles  used  as  such,  concern  the  health  of 
those  who  use  them  and  put  dependence  upon  them.  By  action  or 
failure  of  action,  a  medicine  is  liable  to  prove  hurtful  when  mis- 
applied. Therefore,  it  is  the  right  of  a  purchaser  of  a  medicine  to 
receive  information  of  its  constituents,  their  names  and  propor- 
tional quantities.  And  it  is  a  legitimate  act  of  the  State — so  far  as 
it  deems  expedient — to  see  to  it  that  such  information,  in  printed 
form,  is  placed  upon  each  package  of  articles  of  medicine,  as  a 
condition  of  their  legal  sale. 

"  Moreover,  legislation  requiring  the  composition  of  medicines 
to  be  given  to  the  consumer  is  entirely  in  accord  with  the  spirit  of 
the  institutions  of  the  United  States,  because  it  is  legislation  tending 
to  secure  him  in  the  means  of  self-preservation.  The  purchaser  of 
a  medicine  is  provided  with  a  record  of  its  constituents,  given  in 
terms  defined  by  published  standards:  now  he  may  guide  himself, 


260 


The  Patent  Medicine  Problem.  {KmjnlT\luvtsx' 


in  his  own  discretion  or  with  professional  aid,  by  the  information 
given  in  the  record  of  constituents,  or  he  may  neglect  to  so  guide 
himself,  and  depend  upon  advice  given  on  the  wrapper  of  the 
medicine,  in  the  exercise  of  his  personal  responsibility.  The  State 
has  done  its  duty,  and  given  the  individual  the  opportunity  for  the 
exercise  of  discretion.  The  opportunity  has  an  educational  value  to 
the  individual." 

The  following  year  the  Committee  on  Legislation,  in  its  report  of 
progress  (Proc.  Am.  Pharm.  Assoc.,  1886,  v.  34,  p.  10,  154,  155), 
included  a  resolution  to  the  effect  that : 

"  Whereas,  All  medicines  concern  the  health  of  those  who  use 
them;  and 

4k  Whereas,  The  purchaser  of  a  medicine  selected  by  himself 
has  the  right  to  receive  information  of  its  constituents  and  their 
quantities;  and 

"  Whereas,  The  report  and  the  draft  of  a  law  regulating  the 
sale  of  proprietary  medicines,  which  were  accepted  by  the  American 
Pharmaceutical  Association  at  its  meeting  held  in  September,  1855, 
embrace  a  method  whereby  the  above-mentioned  objects  may  be 
secured;  therefore,  be  it 

"  Resolved,  That  the  President  and  other  officers  of  the  Asso- 
ciation be  authorized  and  instructed  to  present  printed  copies  of  the 
reports  and  of  the  action  had  in  this  Association  upon  said  reports, 
to  the  Governors,  to  the  Speakers  of  the  Senates  and  Houses  of 
Representatives,  and  to  the  State  Boards  of  Health,  of  the  different 
States  of  the  United  States ;  also>  to  offer  any  services  wherein  these 
authorities  may  consider  the  cooperation  of  this  Association  desir- 
able or  useful." 

This  preamble  and  resolution  was  vigorously  discussed  and  a 
motion  that  they  be  stricken  from  the  minutes  of  the  Association 
was  defeated.  The  report  of  the  Committee  was  then  on  motion 
accepted,  and  finally  on  motion  of  C.  Lewis  Diehl,  seconded  by  C. 
S.  N.  Hallberg,  the  preamble  and  resolution  were  adopted. 

Despite  the  endorsement  given  the  report  of  the  Committee  on 
Legislation,  little  or  nothing  of  a  practical  nature  appears  to  have 
been  done.  During  the  early  years  of  the  succeeding  decade  a  few 
isolated  papers  on  patent  medicine  abuses,  from  a  public  health  point 
of  view,  were  presented,  but  their  readers  found  no  following  and  the 
resolutions  they  offered  appear  to  have  been  overlooked  or  ignored, 
while  much  of  the  time  of  the  Association  was  devoted  to  the  dis- 


Am  Jour  Pharm.)        The  Patent  Medicine  Problem.  261 

June,  iyi4:.  j 

cussion  of  a  plan  or  plans  to  remedy  the  "  cutting  of  prices."  The 
seriousness  with  which  time  was  wasted  on  the  discussion  of  the 
several  plans  that  were  suggested  at  that  time  serves  well  to  illus- 
trate the  comparative  importance  that  has  been  accorded  the  purely 
economic  side  of  this  problem  by  various  branches  of  the  drug  trade. 

At  the  semi-centennial  meeting  of  the  American  Pharmaceutical 
Association,  in  1902,  several  papers  were  again  presented,  bearing 
on  existing  abuses  in  connection  with  patent  and  proprietary  reme- 
dies. These  papers  dealt  principally  with  the  abuse  of  so-called 
proprietary  medicines  and  their  use  by  physicians,  and  perhaps  con- 
tributed somewhat  at  least  to  the  renewed  interest  on  the  part  of  the 
American  Medical  Association  in  matters  relating  to  the  use  of 
secret  or  semi-secret  remedies  by  medical  practitioners. 

At  the  meeting  of  the  American  Medical  Association  in  New 
Orleans  in  1903,  a  number  of  papers  were  presented  criticising 
medical  journals  for  the  nature  and  kind  of  advertising  carried  by 
them,  and  a  resolution  adopted  by  the  then  Section  on  Materia 
Medica  and  Pharmacy  condemned  much  of  the  advertising  then  car- 
ried in  the  Journal  of  the  Association  itself.  At  this  meeting  of  the 
Association  provision  was  also  made  for  pharmaceutical  member- 
ship in  the  American  Medical  Association,  and  at  the  meeting  in 
Atlantic  City  the  following  June  a  number  of  pharmacists  were 
elected  and  the  discussions  on  materia  medica  subjects,  with  the 
resolutions  adopted  at  Atlantic  City  in  1904,  no<  doubt  were  directly 
responsible  for  the  inauguration  of  a  Council  on  Pharmacy  and 
Chemistry,  the  object  of  which  was  to  endeavor  to  differentiate 
between  good  and  bad  proprietary  remedies  used  by  or  offered  to 
physicians. 

A  preliminary  meeting  of  persons  interested  was  held  in  Phila- 
delphia on  December  29,  1904,  and  the  Council  itself  was  organized 
in  Pittsburg  on  February  11,  1905.  This  Council  was  immediately 
set  to  work  and  by  June  of  the  same  year  the  comprehensive  and  at 
that  time  startling  report  on  the  acetanilide  mixtures  was  published 
in  the  Journal  of  the  American  Medical  Association  and,  as  was 
expected,  precipitated  the  wrath,  not  alone  of  pharmaceutical  manu- 
facturers, but  also'  of  medical  journals  that  depend  so  largely  on 
their  advertising  pages  for  existence.  The  so-called  acetanilide  re- 
port served,  however,  to*  arouse  the  better  class  of  medical  men  to 
an  appreciation  of  their  duty  as  professional  men  and  the  endorse- 


262  The  Patent  Medicine  Problem.       {Am  j^iqw!™' 

ment  thus  secured  has  contributed  much  to  maintain  the  Council 
despite  the  attacks  of  moneyed  interests  within  and  without  the 
membership  of  the  Association. 

The  work  of  the  Council  was  later  in  the  year  efficiently  aug- 
mented by  the  series  of  articles  originally  published  in  Collier's 
Weekly,  by  Samuel  Hopkins  Adams,  on  the  "  Great  American 
Fraud,"  and  subsequently  reprinted  in  pamphlet  form  by  the  Amer- 
ican Medical  Association.  The  Food  and  Drugs  Act  of  June  30, 
1906,  also  contributed  its  share  in  support  of  the  work  of  the  Council. 
These  several  agencies  have  been  further  augmented  by  the  stand 
taken  by  the  Commissioner  of  Internal  Revenue  in  regard  to  alcohol 
containing  nostrums  and  by  the  assistance  given  by  various  state 
officials  entrusted  with  the  enforcement  of  local  food  and  drug  laws, 
so  that  at  the  present  time  there  is  considerable  evidence  to  show 
that  the  efforts  of  the  Council  on  Pharmacy  and  Chemistry  have 
made  a  distinct  impression  on  thinking  laymen  as  well  as  on  the 
more  progressive  members  of  the  American  Medical  Association. 

Following  the  inauguration  of  the  Council  on  Pharmacy  and 
Chemistry,  the  American  Medical  Association  organized  a  chemical 
laboratory  in  the  Association  building,  and  this  laboratory,  in  addi- 
tion to  the  work  on  "proprietary  remedies,"  has  devoted  consider- 
able time  to  the  examination  of  so-called  "  patent  medicines  "  or 
4t  nostrums."  The  resulting  analyses  are  usually  published  in  the 
Journal  and  have  been  in  part,  at  least,  compiled  in  book  form  in  a 
volume  entitled  "  Nostrums  and  Quackery." 

This  book  has  recently  been  reprinted  in  enlarged  form,  and  its 
increasing  circulation  among  well-informed  laymen  will  contribute 
much  to  a  better  understanding  of  the  patent  medicine  problem  from 
a  public  health  point  of  view,  and  should  serve  to  prevent  any  pos- 
sible retrogressive  action  on  the  part  of  the  American  Pharmaceu- 
tical Association  as  an  Association. 

In  summing  up  this  brief  and  admittedly  incomplete  survey  of 
recent  accomplishments  to  solve  the  "  patent  medicine  "  problem,  it 
would  appear  that  the  questions  involved  are  not  to  be  considered 
as  being  answered  until  they  are  answered  correctly,  and  that  from 
the  point  of  view  of  the  public  the  influence  of  "  patent  medicines  " 
on  the  health  and  welfare  of  the  individual  is  the  only  factor  deserv- 
ing of  consideration.  Bearing  this  latter  fact  in  mind,  it  would 
appear  desirable  that  all  branches  of  the  drug  trade  give  the  patent 


Am'j^ne,r'i9Pi4arm'}  Plea  for  More  Effective  C 'ooperation.  263 

medicine  problem  renewed  and  serious  consideration,  and  make  an 
honest  effort  to  adjust  their  interests  in  accord  with  the  interests  of 
the  public  and  thus  effectually  counteract  the  frequently  made  asser- 
tion that  the  economic  questions  involved  must  outweigh  all  others 
so  far  as  the  drug  trade  may  be  concerned. 


A  PLEA  FOR  MORE  EFFECTIVE  CO-OPERATION  AMONG 
PHARMACEUTICAL  ORGANIZATIONS. 

By  W.  B.  Day. 

Even  a  superficial  observer  of  pharmaceutical  affairs  must  have 
been  struck  by  the  increase  in  the  number  of  organizations  which 
depend  upon  pharmacists  for  their  membership.  Not  only  have  we 
the  two  great  national  associations  but  each  commonwealth  is  more 
or  less  thoroughly  organized  with  its  state,  county  and  city  associa- 
tions. 

At  first  glance  this  situation  appears  most  encouraging  and  seems 
to  show  an  appreciation  of  the  value  of  these  organizations  and  a 
commendable  spirit  in  affiliating  with  them  and  sharing  their  en- 
deavors and  their  advantages,  but  when  we  look  into  the  matter 
more  closely  we  find  that  with  all  these  opportunities  for  affiliation 
with  an  active  society,  the  majority  of  pharmacists  remain  indifferent. 

There  are  nearly  fifty  thousand  drug  stores  in  the  United  States 
and  probably  over  seventy-five  thousand  qualified  pharmacists.  Less 
than  five  per  cent,  of  these  are  members  of  the  American  Pharma- 
ceutical Association,  and  certainly  not  more  than  twenty  per  cent, 
are  members  of  the  National  Association  of  Retail  Druggists.  Very 
few  state  associations  include  within  their  membership  more  than 
a  fifth  of  the  qualified  pharmacists  of  their  respective  states. 

In  some  of  the  larger  cities  strong  local  associations  exist,  but,  on 
the  other  hand,  there  are  many  counties  and  cities  where  organiza- 
tion has  never  been  effected,  or  if  effected  has  perished  through  dis- 
use and  neglect.  Contrast  with  this  'the  situation  in  Great  Britain, 
where,  of  all  European  countries,  the  conditions  most  resemble  our 
own.  The  last  report  of  the  Registrar  of  the  Pharmaceutical  Society 
of  Great  Britain  shows  7788  members  out  of  16,608  qualified  phar- 
maceutical chemists  and  chemists  and  druggists.  Allowing  for  those 
who  have  retired  from  business  or  are  engaged  in  some  other  line 


264  Plea  for  More  Effective  Cooperation.  |Am- jJu0"er- ^ rm 

of  work,  it  is  estimated  that  nearly  two-thirds  of  the  chemists  and 
druggists  of  Great  Britain  are  members  of  the  national  society.  And 
the  membership  is  growing  steadily ;  the  increase  has  been  twenty- 
five  per  cent,  during  the  last  ten  years. 

The  only  reason  for  the  existence  of  any  organization  is  service  to 
its  members  and  to  the  profession  which  it  represents.  Are  present 
conditions  favorable  to  such  service?  Is  there  not  a  wasteful  dupli- 
cation of  effort?  Should  there  not  be  a  better  correlation  of  or- 
ganized pharmaceutical  activities? 

Pharmaceutical  associations  have  done  wonderfully  well  in  leg- 
islation, in  education,  in  the  development  of  scientific  pharmacy  and 
in  the  spreading  of  a  knowledge  of  both  technical  and  business 
methods.  Co-operation  has  solved  many  perplexing  questions : 
dangers  have  been  bravely  faced,  evils  have  been  overcome,  and  yet 
a  start  has  scarcely  ]  en  made. 

The  attention  of  pnarmacists  has  often  been  called  to  the  chang- 
ing conditions  which  vitally  affect  our  calling.  Not  only  are  these 
evidenced  by  the  spread  of  commercialism,  the  development  of  chain 
stores  and  syndicates,  the  increased  dispensing  by  physicians  and  the 
multiplication  of  hospitals  and  dispensaries,  but,  deeper  than  these — 
the  drift  of  social  legislation  which  in  Great  Britain  has  produced 
the  National  Insurance  Act  and  in  Germany  has  resulted  in  a  state- 
controlled  industrial  insurance.  We  may  as  well  face  the  possibility, 
if  not  the  probability,  of  state-paid  medical  service,  including  state- 
furnished  medicines  in  our  own  country,  during  the  next  generation. 
Judging  from  the  lack  of  recognition  accorded  to  pharmacists  in 
our  army,  we  are  held  in  but  low  esteem  by  the  federal  government 
at  the  present  time ;  physicians,  dentists  and  even  veterinarians  rank 
far  above  us  in  the  largest  arm  of  the  government  service. 

It  is  high  time  that  all  pharmaceutical  organizations  should  care- 
fully consider  a  general  affiliation  and  correlation  such  as  shall 
assign  to  each  its  special  field  and  avoid  the  present  overlapping  and 
duplication.  More  effective  work  will  be  possible  only  through  such 
mutual  relations,  and  will  deserve  and  receive  wider  support  by 
pharmacists.  A  united  body  of  seventy-five  thousand  pharmacists 
would  command  respect  and  insure  fair  treatment  in  the  coming  re- 
adjustment and  division  of  labor  that  is  sure  to  come  as  a  part  of 
the  social  movement. 


University  of  Illinois  School  of  Pharmacy. 


Am.  Jour.  Pharm. 
June,  1914. 


Efficiency  in  Drug  Stores. 


265 


EFFICIENCY  IN  DRUG  STORES. 
By  C.  C.  Honsaker,  P.D. 

This  is  the  age  of  specialization.  Lawyers,  doctors,  mechanics 
and  ministers  are  specialists ;  when  needed  they  are  consulted,  they 
need  and  consult  one  another.  We  all  recognize  that  no  one  man 
knows  it  all.  Just  as  there  are  sick  people  that  need  competent 
counsel,  so  there  are  sick  businesses  that  need  attention  from  experts. 

The  old  time  business  expert  was  and  is,  in  fact,  somewhat  like 
the  old-time  doctor.  He  administered  tonics  and  palliatives  instead 
of  getting  at  the  seat  of  trouble. 

By  keeping  records  and  making  tests,  chemists,  pharmacists  and 
physicians  have  been  able  to  standardize  certain  medicines. 

It  has  been  but  recent,  however,  that  the  b  .mess  doctor  was  able 
to  diagnose  and  apply  a  standardized  remedy,  or  specific,  to  a  sick 
business. 

This,  however,  has  been  accomplished  by  the  two  great  efficiency 
engineers,  Emerson,  of  New  York,  and  Taylor,  of  Philadelphia. 
These  men  have  gathered  together  the  threads  of  activity,  and  woven 
them  into  the  science  known  as  efficiency.  Efficiency  means  the 
ability  to  accomplish.  Personal  efficiency  is  the  mental  and  physical 
ability  to  find,  and  take,  the  best,  easiest,  and  quickest  way  to  the 
desirable  things  of  life. 

These  principles  are  not  new,  you  and  I  employ  them  every  day, 
at  least  some  of  them. 

Just  as  Sheldon  has  analyzed  the  sale,  so  has  Emerson  analyzed 
the  operations  and  procedures  of  hundreds  of  successful  men,  and 
found  that  thirteen  (13)  principles  were  involved,  in  part  or  whole, 
by  them  in  their  accomplishments. 

There  are  seven  (7)  practical  principles,  and  six  (6)  ethical  ones. 
To-day  we  will  be  concerned  with  the  practical  ones  only. 

A  sick  business  like  a  sick  body  always  has  one  symptom  that 
gives  the  most  trouble,  from  which,  tracing  backward,  the  cause  can 
be  located  by  the  trained  expert  You  all  know  what  this  symptom 
of  unscientific  business  is  in  the  drug  world.  The  rancorous  sore  in 
the  side  of  the  drug  business  is  the  long  hours.  This,  however,  is 
only  a  symptom  or  effect.   The  cause  is  much  deeper. 

This  thirteen  (13)  to  fifteen  (15)  hour  day  is  driving  the  best 


266 


Efficiency  in  Drug  Stores. 


Am.  Jour.  Pharm 
June,  1914. 


men  out  of  the  business.  The  great  cry  of  the  retail  druggist  is, 
"  that  we  cannot  get  competent  men." 

The  P.  C.  P.  and  other  colleges  give  men  good  scientific  training, 
which  most  of  them  never  have  an  opportunity  to  use.  The  drug 
journals  contain  article  after  article  about  building  up  business; 
these  are  read,  possibly,  but  seldom  put  into  actual  practice.  The 
various  organizations  ask  for  action  and  attendance,  but  get  little 
or  none,  although  the  advantages  to  be  gained  are  obvious.  Tradi- 
tion has  established  a  routine  in  the  drug  store,  which  very  few  have 
been  able  to  break  away  from,  and  those  who  do  are  usually  con- 
demned. 

There  is  no  hope  for  the  man  who  works  thirteen  (13)  to  fifteen 
(15)  hours  a  day.    It's  a  losing  game  every  way  one  looks  at  it. 

The  philosophy  of  the  business  must  be  changed.  It  must  be 
studied  from  the  standpoint  of  the  sale. 

Business  is  buying  and  selling.  Selling  is  our  objective  point. 
Our  drugs  and  merchandise  must  be  organized  toward  making  the 
sale.  The  sale  is  the  point  from  whence  the  money  comes.  Sales 
and  quick  ones.  The  five  (5)  and  ten  (10)  cent  stores  are  based  on 
the  principle  of  small,  quick  sales.  Your  average  sale  in  the  drug 
store  is  from  fifteen  (15)  to  eighteen  (18)  cents. 

Efficiency,  then,  is  the  keynote.  It  is  the  only  salvation.  Mr. 
Emerson  would  probably  try  to  pull  the  manager  out  of  the  mass  of 
details  first,  so  that  he,  the  manager,  could  get  a  perspective  of  his 
business.  So  we  will,  on  that  assumption,  try  and  apply  the  seven 
(7)  principles  to  the  manager  first,  since  a  business  is  but  the  length- 
ened shadow  of  a  single  individual. 

There  is  one  thing  that  the  druggist  is  fortunate  in  having,  and 
that  is  twenty- four  (24)  hours  a  day.  The  trouble  is  that  he  does 
not  use  it  advantageously.  Twenty-four  (24)  hours,  then,  is  a  fixed 
quantity,  fixed  and  unchangeable.  Time  is  what  we  are  trying  to 
save,  therefore  we  will  use  it  as  our  basis. 

Standards. 

The  first  principles  of  scientific  management  is  "  Standards."  A 
standard  is  a  reasonable  attainable  maximum  of  desirability.  Before 
standards  can  be  established,  however,  many  records  must  be  made. 

A  record  is  anything  that  gives  information  of  any  kind.  Records 
play  an  important  part  in  everything  we  do.  Baseball  furnishes  an 
excellent  example  of  the  use  of  records. 

What  we  want,  then,  is  a  record  of  what  the  druggist  does  with 


Am.  Jour.  Pharm. 
June,  1914. 


Efficiency  in  Drug  Stores. 


267 


his  fourteen  (14)  hours  each  day.  This  is  accomplished  by  the  use 
of  a  special  chart,  conveniently  divided  into  five  (5)  minute  periods 
or  squares.  The  efficiency  engineer  keeps  an  account  of  every  five 
(5)  minutes  of  the  fourteen  (14)  hours,  for  a  period  of  time,  say 
for  one  (1)  week.  At  the  expiration  of  the  allotted  time  the  various 
minutes  are  classified,  wasted  time  analyzed,  and  a  standard  estab- 
lished for  each  of  the  various  operations. 

Possibly  he  filled  fifty  (50)  prescriptions  during  the  week  and 
expended  approximately  thirteen  (13)  hours.  The  standard  time, 
then,  for  filling  one  (1)  prescription  is  fifteen  (15)  minutes  under 
normal  conditions. 

You  will  say  that  it  is  impossible  to  establish  a  standard  for  such 
a  changeable  and  indefinite  operation.  That  is  what  they  all  say. 
If  it  were  easy  it  would  have  been  done  long  ago.  It  can  be  done 
with  a  complex  operation,  having  many  factors,  as  well  as  with  the 
simpler  operations,  such  as  shoveling,  shaving  or  even  writing  your 
name. 

You  now  have  an  annotated  topography  of  your  duties.  Your 
next  move  is  to  organize  the  operations  into  logical  sequence.  That 
brings  us  to  the  second  principle. 

Planning. 

You  now  plan  your  operations.  This  you  can  do  intelligently, 
since  you  are  dealing  with  known  facts.  At  this  point  of  the  reorgani- 
zation your  business  policy  changes.  You  become  the  power  behind 
the  business.  The  customer,  doctor,  salesman  and  others  cease  to 
mould  your  business  to  suit  them.  You  are  becoming  aggressive. 
You  know  how  long  it  takes  to  make  a  sale.  You  make  the  sale 
and  get  away.  The  salesmen  come  and  go  when  you  say ;  not  when 
they  want  to. 

To  plan,  though,  is  not  enough.  The  Pennsylvania  Railroad 
might  plan  to  run  the  twentieth  century  limited  from  New  York  to 
Chicago;  but,. unless  schedules  were  made,  this  plan  would  be  use- 
less. One  crew  might  run  at  breakneck  speed  and  send  the  train  to 
the  junk  pile;  another  so  slow  as  to  consume  unnecessary  fuel.  So, 
in  order  to  avoid  those  conditions,  definite  schedules  are  carefully 
made.    Consequently,  the  next  principle  to  be  applied  is  schedules. 

Schedules. 

A  plan  is  a  general  statement. 

A  schedule  is  a  definite  itemized  statement. 

So,  now,  each  operation  is  looked  after  minutely,  a  definite  time 


268 


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Am.  Jour.  Pharm. 
June,  1914.  M 


for  its  beginning  and  completion  established.  Everything  in  the 
store  is  now  beginning  to  organize  itself  toward  carrying  into  effect 
this  new  element  of  activity.  Everything  must  fall  in  line.  You 
do  not  wait  for  anything.  Your  motive  is  based  upon  known  facts, 
and  you  know  that  you  are  right. 

To  be  scientific  there  must  be  a  way  of  showing  results.  There 
is,  and  it  is  calculated  by  the  following  method. 

Divide  the  actual  number  of  hours  employed  by  the  standard 
number,  and  the  result  is  your  efficiency  of  supply,  e.g.,  say  the  time 
wasted  by  various  leaks  to  be  three  hours,  and  your  standard  is 
fourteen  hours,  the  actual  number  of  hours  employed  is  the  differ- 
ence between  fourteen  hours  and  three  hours,  or  eleven  hours.  This 
eleven  hours  divided  by  the  fourteen  hours  gives  78,  your  per  cent, 
of  efficiency  of  supply. 

However,  a  man  may  be  100  per  cent,  efficient  in  supply  of  time, 
and  yet  not  be  efficient  in  the  use  of  time,  e.g.,  a  pharmacist  spends 
thirty  minutes  in  compounding  one  prescription.  His  standard  ac- 
complishment for  thirty  minutes  is  two  prescriptions.  Actual 
accomplishment,  which  is  one  prescription,  divided  by  standard 
accomplishment,  which  is  two  prescriptions,  shows  his  usage  of 
time  to  be  50  per  cent. 

These  same  principles,  remember,  apply  to  equipment  and 
material  as  well  as  time.  You  may  be  efficient  in  supply  and  not  in 
use.  You  may  be  efficient  in  use  and  not  in  supply.  You  attain 
maximum  efficiency  only  when  you  are  efficient  in  both.  This  is 
calculated  as  end  efficiency.  End  efficiency  is  computed  by  multi- 
plying your  supply  of  time  efficiency  by  your  efficiency  of  use. 

The  next  principle  is  despatching. 

Planning,  as  you  have  seen,  means  looking  ahead,  deciding  what 
is  to  be  done,  how  much  time  is  to  be  allotted  the  stunt,  and  what 
material  and  equipment  are  necessary  to  its  accomplishment. 

Schedules  assign  to  each  stunt  a  definite  time  and  place,  and 
definite  quantities  and  qualities  of  material.  They  also  list  the 
equipment  necessary,  both  as  to  quantity  and  place,  and  the  standard 
time  for  the  operation  of  equipment.  It  is  not  enough  to  establish 
standards  for  time,  material  and  equipment.  It  is  not  enough  to 
plan  ahead.  It  is  not  enough  to  write  schedules,  no  matter  how 
elaborate  and  perfect  they  may  be. 

You  must  have  action.  In  other  words,  the  work  or  stunt  must 
be  despatched.    Some  of  the  well  known  examples  of  despatching 


Am.  Jour.  Pbarm. 

Juue,  1914. 


Efficiency  in  Drug  Stores. 


269 


are  the  umpires  at  a  professional  baseball  game,  the  directing  "  next  " 
of  a  porter  in  the  barber  shop,  and  the  train  despatcher. 

The  antithesis  to  despatching  is  procrastination. 

Procrastination  is  nearly  always  due  to  a  tired  body  or  brain ; 
again,  the  accusing  finger  points  to  the  long  hours.  How  can  a  man 
despatch  an  important  operation  or  communication  who  is  submerged 
by  multifarious  details?  A  train  despatcher  as  well  as  an  umpire 
must  be  up  and  above  the  thing  he  is  directing. 

Connie  Mack's  method  of  directing  from  the  bench  is  better 
than  the  old  style  of  directing  from  the  field. 

The  principle  of  despatching  is  a  simple  one.  It  means  that 
when  the  time  comes  to  do  a  thing  you  should  have  everything  on 
hand  and  prepared  to  do  it,  and  do  it. 

Standardising  conditions. 

This  is  the  fifth  principle  of  efficiency.  This  is  the  principle 
which  is  universally  misapplied  and  misconstrued  to  mean  efficiency. 
Mention  efficiency  to  the  average  druggist  and  he  will  tell  you  that 
he  has  the  most  efficient  store  in  town.  What  he  means  is  that  he 
has  systematized  his  store  from  a  certain  standpoint.  Efficiency 
implies  system,  but  system  does  not  by  any  means  imply  efficiency. 
YoU  can  do  a  thing  systematically  wrong. 

From  the  moment  the  first  principle  is  applied  you  began  re- 
arranging and  standardizing  conditions.  This  is  an  indication  of  the 
interdependence  of  the  thirteen  principles. 

By  learning  each  of  the  thirteen  principles  you  apply  the  fifth 
principle  consciously,  and,  therefore,  more  fully  and  effectively. 

There  must  be  a  place  for  everything,  but  that  place  can  only  be 
found  after  many  trial  conditions.  At  this  point  I  wish  to  call  your 
attention  to  the  greatest  loss  in  the  drug  business.  The  druggist 
finds  himself  doing  many  things  which  could  be  done  by  subordi- 
nates ;  such  as  dusting,  running  errands,  looking  up  phone  numbers, 
selling  stamps,  dispensing  soda  water,  etc.  While  learning  the 
business  he  did  not  mind  doing  it,  because  he  looked  forward  to  the 
time  when  he  would  take  on  larger  responsibilities.  The  time  came 
with  the  responsibilities,  but  the  menial  labor  remained  just  the  same. 
How  can  a  man,  who  fills  the  capacity  of  a  menial,  command  respect? 
Justice  to  all  includes  justice  to  self. 

There  are  thousands  of  five  and  ten  cent  sales  made  in  the  drug 
store.  You  cannot  afford  to  waste  energy  making  them.  They  must 
sell  themselves.    They  are  what  might  be  termed  trailers,  such  as 


270 


Efficiency  in  Drug  Stores. 


{ Am.  Jour.  Pharm 
\     June,  1914. 


corn  cures,  epsom  salts,  seidlitz  powders,  etc.  You  can  only  afford 
to  spend  energy  on  larger  sales. 

This  capacity  to  assign  yourself,  subordinates,  material,  etc.,  is 
calculated  as  efficiency  of  assignment.  Consult  your  records,  find 
the  most  profitable  hour  of  employment.  This  is  your  standard 
worth  for  an  hour.  For  example,  suppose  that  for  a  given  hour 
your  efficiency  of  supply  was  91.7  per  cent.;  in  other  words,  that 
you  profitably  employed  forty-five  minutes  out  of  the  sixty  in  that 
hour.  Your  efficiency  of  use  was  85  per  cent. ;  in  other  words,  you 
folded,  labelled  and  packed  eighty-five  seidlitz  powders  during  that 
hour,  where  your  standard  number  for  that  hour  should  have  been 
one  hundred.  The  end  efficiency  of  supply  and  use,  therefore,  was 
eighty-hundredths  of  91.7  per  cent.,  or  about  78  per  cent.  Since  a 
girl  might  have  folded,  labelled  and  packed  those  eighty-five  powders 
in  forty-five  minutes,  and  her  wages  for  the  forty-five  minutes  would 
have  been  twenty  cents,  the  actual  commercial  value  of  what  you 
accomplished  during  that  hour  was  twenty  cents.  For  the  purpose 
of  illustration,  let  us  fix  your  standard  worth  at  $1.00  for  the  hour. 
Twenty  cents  is  20  per  cent,  of  $1.00;  this  is  your  efficiency  of 
assignment  for  that  hour.  Your  end  efficiency  for  supply,  use,  and 
assignment  is  therefore  85  x  91.7  x  20  per  cent.,  or  15.5  per  cent. 

Efficiency  of  assignment  is  measured  by  the  ratio  between  actual 
value  of  what  is  accomplished  or  produced  in  a  given  time  or  from 
a  given  material  or  a  given  equipment  and  the  standard  value  of 
production  for  such  time,  material  or  equipment. 

All  the  work  in  learning  and  applying  the  first  five  practical  prin- 
ciples of  efficiency  has  been  not  only  leading  up  to  the  sixth  prin- 
ciple, but  actually  compelling  you  to  apply  it. 

The  sixth  principle  is  standardized  operations. 

It  is  obvious  that  there  is  only  one  best,  easiest  and  quickest  way 
to  do  any  given  thing. 

There  may  be  one  hundred  different  ways  of  doing  a  thing.  This 
brings  the  case  under  the  mathematical  law  of  probability.  The 
chance  that  you  may  happen  upon  the  one  best,  easiest  and  quickest 
way  is  only  one  in  a  hundred.  To  show  how  slight  are  the  chances 
of  happening  to  choose  the  right  operation,  Mr.  Emerson  cites  the 
case  of  an  executive  whose  work  he  was  called  upon  to  study.  This 
man's  working  day  was  fifteen  hours,  and  he  was  always  "  terribly 
busy."  As  he  did  not  plan  his  work,  but  simply  turned  feverishly 
from  one  task  to  another  as  they  presented  themselves,  he  wasted 


Am.  Jour.  Pharm. 
June,  1914. 


Efficiency  in  Drug  Stores. 


271 


twenty-five  per  cent,  of  his  time.  This  reduced  his  efficiency  of 
supply  to  75  per  cent. 

Because  he  worked  too  many  hours  a  day  to  maintain  a  standard 
condition  of  health  and  mental  vigor,  he  not  only  procrastinated, 
dragged  his  work  and  kept  others  waiting,  but  made  many  blunders. 
The  correction  of  these,  where  correction  was  at  all  possible,  con- 
sumed a  great  deal  of  time.  Taking  into  consideration  his  slow 
accomplishment,  subtracting  the  amount  of  time  wasted  in  correct- 
ing blunders,  and  the  amount  of  time  consumed  in  doing  things 
wrongly,  which  could  not  be  corrected,  his  efficiency  of  use  was 
greatly  reduced.  Since  he  was  too  busy  and  too  harassed  to  plan 
his  work,  he  did  not  standardize  any  of  his  conditions  or  operations, 
leaving  these  matters  entirely  to  chance,  with  the  result  that  his 
efficiency  of  use  of  time  was  only  60  per  cent.  Because  he  did  not 
plan  or  study,  it  naturally  resulted  that  he  spent  a  great  deal  of  his 
time  doing  unnecessary  things,  as,  for  example,  keeping  records, 
that  were  neither  immediate,  reliable,  adequate  nor  permanent.  He 
also  wasted  hours  blundering  along  with  trivial  details  that  ought 
to  have  been  unloaded  upon  a  subordinate  who  would  have  done  them 
far  more  efficiently. 

For  these  reasons-  his  efficiency  of  assignment  was  only  40  per 
cent.,  and  his  end  efficiency  (75  x  60  x  40)  was  18  per  cent.  By 
means  of  the  thirteen  principles  of  efficiency  he  might  have  accom- 
plished just  as  much  with  far  better  quality  in  three  hours  as  he 
had  been  accomplishing  in  fifteen  hours.  You  know  an  analogous 
case. 

To  get  back  to  standardized  operations.  This  is  the  phase  of 
efficiency  that  you  mostly  read  about  in  the  magazines;  it  involves 
time  and  motion  study. 

Without  going  into  detail,  I  have  tried  to  give  you  a  perspective 
of  the  application  of  the  principles  of  efficiency.  This  skeletonized 
elucidation  leaves  many  questions  unanswered  that  will  naturally 
arise  in  your  mind  concerning  their  application  to  the  drug  busi- 
ness. You  may  not  be  able  to  see  how  they  could  possibly  be  appli- 
cable in  the  face  of  so  many  uncertainties,  such  as  occur  in  the  drug 
business. 

Like  a  Socialist  I  answer  by  saying  that  those  uncertain  obstacles 
would  not  exist  under  proper  management.  The  drug  business 
to-day  is  governed  by  outside  influences.  The  task  we  have  is  to 
regain  control  and  manage  according  to  a  definite  business  policy. 


272 


Progress  in  Pharmacy. 


f  Am.  Jour.  Pharm. 
\      June,  1914. 


You  do  not  know  what  to  charge  for  a  prescription,  because  you 
have  not  standardized  the  operation  of  compounding.  It  is  difficult, 
that  is  why  it  has  not  been  done,  but  it  can  be  done. 

The  seventh  and  last  practical  principle  is  written  standard  prac- 
tice instructions.  School  text  books,  periodicals  and  the  pharma- 
copoeia are  written  standard  practice  instructions. 

It  is  a  difficult  thing  to  change  one's  style  of  doing  anything; 
therefore,  it  is  necessary  to  strike  a  form,  and  to  do  this  definite 
instructions  must  be  carefully  followed  until  it  can  be  done  with 
little  or  no  conscious  effort. 

PROGRESS  IN  PHARMACY. 

A  Quarterly  Review  of  Some  of  the  More  Interesting  Litera- 
ture Relating  to  Pharmacy  and  Materia  Medica. 

By  Martin  I.  Wilbert,  Washington,  D.  C. 

Interest  in  matters  relating  to  pharmacy  appears  to  be  about 
equally  divided  between  progress  in  the  revision  of  the  Pharmaco- 
poeia of  the  United  States  and  matters  relating  to  legislation  designed 
to  further  restrict  the  sale  of  opium,  cocaine,  and  other  potent  or 
habit- forming  drugs. 

Two  additional  instalments  of  abstracts  of  proposed  changes 
with  new  standards  and  descriptions  for  the  United  States  Pharma- 
copoeia, ninth  revision,  have  been  published  and  distributed.  The 
first  of  these,  a  pamphlet  of  59  pages,  designated  Part  II,  embraces 
most  of  the  drugs  of  vegetable  and  animal  origin  and  presents  more 
comprehensive  changes  than  any  one  of  the  other  instalments  of 
changes  so  far  published. 

The  Chemist  and  Druggist,  London  (1914,  vol.  84,  p.  565),  in 
commenting  on  the  proposed  changes  in  the  pharmacognosy  of  the 
U.  S.  P.,  voices  the  opinion  that  the  general  indications  are  that  the 
monographs  in  the  U.  S.  P.  IX  will  be  quite  an  advance  upon  those 
included  in  the  present  Pharmacopoeia. 

Part  III  of  the  abstract  of  proposed  changes  embraces  most  of 
the  waters,  solutions,  spirits,  extracts,  fluidextracts,  resins,  tinctures, 
and  miscellaneous  galenicals.  Pharmacists  generally  will  be  pleased 
to  learn  that  all  of  the  important  changes  proposed  for  the  several 
official  galenical  preparations  can  be  adequately  reflected  in  somewhat 


Am.  Jour.  Pharm. 
June,  1914. 


Progress  in  Pharmacy. 


273 


less  than  29  printed  pages.  This  fact  would  appear  to  indicate  that 
many  of  the  official  formulae  have  been  found  to  be  satisfactory  and 
that  the  members  of  the.  Executive  Committee  of  Revision  have 
exercised  due  care  in  the  making  of  changes. 

Commenting  on  the  recently  published  abstracts  of  laws  regu- 
lating the  production,  sale,  and  Use  of  poisons  and  habit-forming 
drugs  in  this  country,  the  Pharmaceutical  Journal,  London  (1914, 
vol.  92,  p.  278),  says: 

The  poison  legislation  of  the  United  States  consists  of  a  multi- 
plicity of  statutes  of  a  not  very  effectual  character,  and  a  fundamental 
alteration  of  the  law  seems  to  be  desired.  During  the  year  1912- 
19 1 3,  over  forty  State,  territorial,  or  similar  Legislatures  were  in 
session,  and  nearly  if  not  quite  all  of  these  bodies  enacted  some  form 
of  .legislation  designed  directly  or  indirectly  to  affect  the  sale  and 
use  of  poisons.  But,  notwithstanding  this  abundance  of  legislation, 
the  poison  laws  of  the  United  States  are  admittedly  still  far  from 
perfect. 

"  The  Harrison  anti-narcotic  bill,  so-called,  is  still  pending  in 
the  Senate,  with  some  probability  that  the  original  bill  in  a  slightly 
amended  form  will  become  law  during  the  present  session  of  Con- 
gress. It  is  perhaps  unfortunate  that  the  subject  of  Federal  anti- 
narcotic  legislation  has  been  unnecessarily  complicated  by  the  intro- 
duction of  a  number  of  amendments  that  can  in  no  way  assist  in 
developing  the  primary  object  of  the  bill  and  will  at  best  serve  to 
complicate  its  enforcement  should  it  become  law." 

Boy  land  Bill. — The  recently  enacted  New  York  State  law,  known 
as  the  Boylan  Bill,  prohibits  the  sale  of  habit-forming  drugs  except 
on  the  prescription  of  a  licensed  physician,  but  the  provisions  do  not 
apply  to  the  sale  of  domestic  and  proprietary  medicines  actually  sold 
in  good  faith  as  medicines  and  not  for  the  purpose  of  evading  the 
law,  "  providing  such  remedies  or  preparations  do  not  contain  more 
than  two  grains  of  opium,  or  one-fourth  grain  of  morphine,  or  one- 
fourth  grain  of  heroin,  or  one  grain  of  codeine,  or  ten  grains  of 
chloral  or  their  salts  in  one  fluidounce,  or  if  a  solid  preparation  in 
one  avoirdupois  ounce,  nor  to  plasters,  liniments,  and  ointments  for 
external  use  only."  If  the  prescription  calls  for  more  than  four 
grains  of  morphine,  thirty  grains  of  opium,  two  grains  of  heroin, 
six  grains  of  codeine,  or  four  drachms  of  chloral,  the  authority  for 
the  prescription  must  be  verified. — Pharm.  Era,  19 14,  vol.  47,  pp. 
199,  200. 


274 


Progress  in  Pharmacy. 


Am.  Jour.  Pharm. 
June,  1914. 


International  Opium  Conference.  (Editorial.) — Discusses  a  re- 
port on  the  correspondence  respecting  the  second  International 
Opium  Conference.  It  appears  that  Greece  has  refused  to  sign 
without  stating  any  reason,  while  Turkey  has  refused  to  take  any 
part  whatever  in  the  Conference.  Germany  and  Russia  were  also 
not  ready  to  ratify  the  Convention,  although  they  have  signed.  In 
spite  of  these  facts  it  is  claimed  by  the  delegates  that  matters  have 
advanced  considerably  and  that  a  long  step  has  been  taken  toward 
the  attainment  of  unanimity. — C hem.  and  Drug.,  1914,  vol.  84,  p.  458. 

Commenting  on  the  above,  Xrayser  II  (p.  491)  says:  "  The 
Opium  Convention,  like  Mahomet's  coffin,  is  suspended  between 
heaven  and  earth,  and  while  in  that  state  of  suspense  it  is  worthless 
as  an  instrument  for  any  practical  purpose.  But  while  the  Con- 
vention itself  may  fail  as  an  administrative  force,  I  hope  its  educa- 
tional value  will  not  be  lost  sight  of,  and  that  we  as  chemists  will 
do  what  we  can,  each  in  his  own  sphere,  to  limit  the  evils  which  the 
Convention  in  its  essential  features  was  intended  to  abolish.  There 
always  will  be  a  legitimate  demand  for  and  use  of  cocaine  and  mor- 
phine, and  there  will  also  probably  always  be  an  illegitimate  demand. 
If  we  conscientiously  set  ourselves  to  discourage  the  latter  by  a 
judicious  method  of  satisfying  the  legitimate  use  of  these  drugs, 
then  the  evil,  so  far  as  we  are  concerned,  will  be  as  effectually 
scotched  as  it  would  be  by  the  adoption  of  the  most  stringent  legal 
enactments." 

Drug  Addicts. — Brown,  Lucius  P.,  is  quoted  as  saying:  "  The 
anti-narcotic  law  going  into  effect  recently  is  serving  to  uncover  a 
terrible  state  of  affairs.  Already  we  have  issued  1360  permits  in  the 
State,  a  large  proportion  of  these  to  Nashville  people,  allowing 
druggists  to  sell  them  narcotics  for  habit  use.  While  one-quarter 
of  a  grain  twice  a  day  is  sufficient  for  the  non-user  of  morphine,  it 
requires  eight  grains  daily  for  the  person  with  the  habit.  Those  who 
are  on  our  books  as  having  permits  use  an  average  of  251  grains  a 
month." — Pharm.  Era,  1914,  vol.  47,  p.  233.  See  also  /.  Am.  M. 
Assoc.,  1914,  vol.  62,  p.  1427. 

Price  Maintenance.  (Editorial.) — Considerable  interest  is  being 
manifested  at  the  present  time  in  H.  R.  13305,  a  bill  introduced  by 
Representative  Stephens,  of  New  Hampshire,  which  is  entitled : 
"  A  Bill  to  Prevent  Discrimination  in  Prices  and  to  Provide  for 
Publicity  in  Prices  to  Dealers  and  to  the  Public."  This  bill  has  been 
endorsed  by  the  American  Fair  Trade  League  and  a  number  of  re- 


Amj^neri9i4rm'}  Progress  in  Pharmacy.  275 

tail  organizations,  and  seeks  to  legalize  contracts  between  manu- 
facturers and  dealers  in  articles  of  commerce  produced  under  a  trade 
mark  or  special  brand.  If  enacted  into  law  the  bill  would  restore  to 
manufacturers  the  rights  supposedly  existing  under  which  the  vari- 
ous contracts  were  developed  in  connection  with  the  sale  of  so-called 
patent  medicine. — Pharm.  Era,  1914,  vol.  47,  pp.  145,  146. 

Annual  Meetings. — The  annual  meetings  of  State  and  National 
Pharmaceutical  Associations  and  of  other  related  organizations  are 
attracting  cpnsiderable  attention.  This  year  the  order  of  holding 
the  two  National  Drug  Association  meetings  will  be  reversed :  the 
1 6th  Annual  Convention  of  Retail  Druggists  is  to  be  held  in  Phila- 
delphia, August  17-21,  and  the  62nd  Annual  Convention  of  the 
American  Pharmaceutical  Association  is  to  follow,  in  Detroit,  August 
24-29,  1914. 

American  Chemical  Society. — The  meeting  of  the  American 
Chemical  Society  was  held  in  Cincinnati,  April  7-10.  Fully  1500 
chemists  attended  and  more  than  150  papers  were  read  before  the 
various  sections. 

Meeting  of  the  American  Medical  Association. — The  meeting  of 
the  American  Medical  Association  this  year  is  to  be  held  in  Atlantic 
City,  July  22-26.  The  preliminary  program  published  in  the  Jour- 
nal, May  16,  1914,  contains  an  unusually  interesting  list  of  promised 
contributions.  The  Section  on  Pharmacology  and  Therapeutics 
will  meet  in  the  gymnasium  of  the  Grammar  School,  on  Ohio  Ave- 
nue, and  the  program  for  this  section,  as  usual,  includes  a  number 
of  papers  of  direct  interest  to  pharmacists.  The  exhibition,  both 
scientific  as  well  as  commercial,  will  be  held  in  the  Atlantic  City 
Exhibition  Building,  corner  of  Kentucky  Avenue  and  the  Board- 
walk. The  scientific  exhibition  particularly  promises  to  be  unusually 
interesting,  in  that  an  effort  will  be  made  to  present  the  material  in 
a  collective  form  so  as  to  be  more  readily  studied. — /.  Am.  M. 
Assoc. ,.1914,  vol.  62,  pp.  1 592-1 609. 

The  Pharmacist  and  Pure  Drugs —A  recent  article  in  Public 
Health  Reports  (1914,  vol.  29,  pp.  1137-1144)  calls  attention  to  the 
reported  results  of  analyses  of  a  number  of  widely-used  drugs  and 
preparations,  and  points  out  that  the  proper  enforcement  of  laws 
designed  to  regulate  the  practice  of  pharmacy,  in  conjunction  with 
pure  drugs  laws,  should  relieve  physicians  and  the  public  of  any 
doubt  as  to  the  composition,  purity,  quality,  and  strength  of  all  drugs 
and  medicinal  preparations  used  in  the  treatment  of  disease.  Any- 


276 


Progress  in  Pharmacy. 


Am.  Jour.  Pharin. 
June,  1914. 


thing  short  of  this  is  a  reflection  on  pharmacy  as  a  calling  and  should 
not  be  tolerated  or  allowed  to  continue. 

Laboratory  Equipment  of  Pharmacists.  (Floyd,  Henry  B.)  — 
Some  of  the  balances  found  in  Washington  drug  stores  were  not  sen- 
sitive to  a  grain,  while  others  required  a  decided  overweight  before 
they  would  operate  at  all.  Many  of  the  weights  used  are  inaccurate,  * 
having  been  allowed  to  corrode  or  to  collect  dirt.  Pharmacists  are 
known  to  use  avoirdupois  and  apothecary's  ounces  interchangeably 
without  regard  to  their  difference.  Glassware,  especially  that  of 
less  experienced  manufacturers,  is  frequently  inaccurate. — /.  Am. 
Pharm.  Assoc.,  1914,  vol.  3,  pp.  569-571. 

Weights  and  Measures.  (Editorial.) — In  enforcing  the  weights 
and  measures  statutes  in  various  States  the  officials  report  some  pecu- 
liar conditions  in  connection  with  the  metrological  equipment  of  drug 
stores.  Of  particular  interest  is  the  fact  that  many  instances  are 
reported  of  over-size  measuring  glasses  and  heavy  weights.  These 
can  be  accounted  for  in  only  one  way :  the  druggist  has  been  imposed 
upon  by  the  dealer  from  whom  the  inaccurate  weights  and  measures 
were  obtained.  It  behooves  pharmacists  to  see  that  their  weights 
and  measures  are  accurate,  and  that  none  but  accurate  weights  and 
measures  are  used.  No  legal  requirement  should  be  necessary  to 
assure  the  proper  weighing  and  measuring  of  the  components  of  a 
prescription. — /.  N.  A.  R.  D.,  19 14,  vol.  18,  pp.  262,  263. 

Annual  Reports  of  the  Chemical  Laboratory  of  the  American 
Medical  Association,  Volume  6. — This  little  book  of  ninety-eight 
pages  presents  a  report  of  the  work  done  from  January  to  December, 
191 3,  and  includes  reprints  of  contributions,  reports  abstracted  from 
the  Journal,  and  reports  not  previously  published.  In  addition  to 
the  work  growing  out  of  the  investigations  by  the  Council  on  Phar- 
macy and  Chemistry,  the  laboratory's  work  includes  the  examination 
of  "  patent  medicines,"  and  the  investigation  of  chemical  questions 
connected  with  the  Propaganda  and  the  Queries  and  Minor  Notes 
work  of  the  Journal. 

"  New  and  Nonofdcial  Remedies/' — A  book  review  of  "  New  and 
Nonofficial  Remedies  "  says  that  this  book  is  a  valuable  work  of 
reference  which  gives  the  gist  of  what  is  known  about  a  great  number 
of  well-known  remedies  and  medicinal  agents. — Pharm.  J.,  1914,  vol. 
92,  p.  576. 

Useful  Drugs.  (Editorial.) — "A  Handbook  of  Useful  Drugs," 
issued  by  the  Council  on  Pharmacy  and  Chemistry  of  the  American 


Am.  Jour.  Pharro. 
June,  1914. 


Progress  in  Pharmacy. 


277 


Medical  Association,  is  a  selected  list  of  important  drugs  suggested 
for  the  use  of  teachers  of  materia  medica  and  therapeutics  and  to 
serve  as  a  basis  for  the  examination  in  therapeutics  by  State  Medical 
Examining  and  Licensing  Boards.  The  great  aim  of  the  compilation 
is  to  eliminate  the  mass  of  useless  or  superfluous  drugs  now  in  books 
on  materia  medica;  it  concerns  products  whose  fixed  value  is  gen- 
erally recognized,  and,  therefore,  it  is  particularly  fitted  to  serve 
as  a  text  on  which  teachers  of  materia  medica  and  therapeutics  may 
base  their  instruction.  *rhe  properties,  pharmacological  action,  ther- 
apeutic uses,  and  dosage  of  drugs  are  discussed  concisely  and  in  a 
practical  manner.  The  methods  of  administration  have  received 
special  attention,  and  there  are  occasional  suggestions  as  to  choice 
of  a  vehicle  which  will  be  of  service  to  beginners  in  prescription 
writing.  There  is  a  table  of  solubilities  of  the  medicaments  in  cold 
water  and  in  cold  alcohol,  a  pharmacological  index,  and  a  general 
index.  The  book  may  be  studied  profitably  by  the  pharmacists  and 
medical  men  of  this  country. — Pharm.  J.,  19 14,  vol.  92,  p.  278. 

Digest  of  Comments. — A  book  review  of  Hygienic  Laboratory 
Bulletin  No.  87,  including  the  Digest  of  Comments  on  the  Pharma- 
copoeia of  the  United  States  of  America,  and  on  the  National  For- 
mulary, for  the  Calendar  year  191 1,  says  in  part:  "  This  volume  is 
a  rich  source  of  references  to  articles  in  various  journals  and  bulle- 
tins dealing  in  any  way  to  the  substances  contained  in  the  American 
Pharmacopoeia,  and  places  the  user  in  position  to  readily  find  the 
original  references  in  which  he  may  be  interested.  The  book  is  a 
model  of  compilation,  such  as  one  would  expect  from  an  international 
pharmacopceial  secretariat." — Pharm.  Weekblad,  1914,  vol.  51,  pp. 
238,  239. 

The  Era  Formulary. — Compilations  of  recipes  for  various  objects 
and  purposes  have  long  been  of  interest  to  the  retail  druggist,  and  few 
stores  in  which  the  ordinary  miscellaneous  drug  business  is  done  can 
be  profitably  conducted  without  one  or  more  books  of  this  type. 
The  new  Era  Formulary  just  published  presents  a  collection  of  nearly 
8000  formulas  gathered  from  recognized  authorities.  The  nine 
divisions  of  the  volume  include  unofficial  .pharmaceutical  prepara- 
tions, toilet  preparations,  veterinary  remedies,  household  remedies, 
paints,  beverages,  and  miscellaneous  preparations  frequently  called 
for  by  the  customers  of  a  live  retail  drug  store.  The  material  was 
compiled  by  William  C.  Alpers  and  Ezra  J.  Kennedy,  and  the  book 
as  published  covers  521  large  8vo  double-column  pages,  including  an 


278  Progress  in  Pharmacy.  {Amjimer'i9uarm* 

index  of  35  pages.  As  a  compendium  of  suggestions  for  the  up-to- 
date  pharmacist  this  book  should  appeal  to  all  pharmacists  who  are 
desirous  of  giving  to  their  patrons  the  best  possible  service  that  they 
are  capable  of. 

Pharmaceutisch  Weekblad. — The  number  of  this  journal  for 
April  3,  19 14,  concludes  the  fiftieth  year  of  the  publication  and  com- 
prises 155  pages  devoted  to  historical  reviews  of  the  progress  of 
pharmacy  during  the  past  fifty  years.  As  a  supplement  the  publishers 
present  a  pamphlet  of  98  pages,  entitled  "  Monumenta  Pharmaceu- 
tical and  containing  a  reprint  of  several  historical  papers  of  phar- 
maceutical interest.  The  first  paper  is  a  reprint  of  the  communica- 
tion by  M.  de  la  Condamine,  "  Sur  l'Arbre  du  Quinquina,"  published 
in  Paris  in  1740.  The  pamphlet  also  contains  a  reprint  of  the  paper 
by  F.  W.  Sertiirner  (1817)  in  which  he  reports  his  discovery  of 
morphine,  a  new  base,  and  of  meconic  acid  as  being  the  principal 
constituents  of  opium.  A  paper  by  Smithson  Tennant  (1814)  on 
the  means  of  producing  a  double  distillation  by  the  same  heat,  a 
paper  by  John  T.  Barry  (1819)  on  a  new  method  of  preparing  phar- 
maceutical extracts,  a  paper  by  Thomas  Thompson  (1818)  on  Mr. 
Henry  Tritton's  patent  for  an  improved  apparatus  for  distillation, 
and  a  paper  on  the  education  of  the  apothecary,  G.  J.  Mulder  (1842), 
are  also  reprinted.  This  supplement  is  exceptionally  interesting,  in 
that  it  makes  available  for  ready  reference  a  number  of  the  more 
important  contributions  to  pharmaceutical  literature. 

Acetyline  is  a  new  name  used  in  some  portions  of  Europe  for 
acetylsalicylic  acid,  and  serves  to  further  complicate  the  nomenclature 
of  this  now  widely  used  substance. — Pharm.  Weekblad,  1914,  vol. 
51,  p.  578.  ^ 

Afridol  is  described  as  sodium  mercuri-o-toluylate,  said  to  be  an 
efficient  substitute  for  corrosive  mercuric  chloride.  Afridol  is  said 
to  be  active  in  dilutions  up  to  1 :  100,000,  while  corrosive  sublimate 
is  no  longer  active  in  solution  of  1 :  50,000. — Sudd.  Apoth.-Ztg., 
1914,  vol.  54,  p.  62. 

Alypin. — Lichtenstein,  L.,  refers  to  the  sudden  fatal  collapse 
after  injection  of  alypin  in  a  case  reported  by  Proskauer  and  one  by 
Ritter.  Schroder  and  Garash  have  also  reported  cases  of  con- 
vulsions, stupor,  and  asphyxia  after  its  use,  and  Lichtenstein  adds 
another  to  this  group. — /.  Am.  M.  Assoc.,  1914,  vol.  62,  p.  975. 

Amorphous  Phosphorus.  (Anon.) — A  criticism  on  the  introduc- 
tion of  amorphous  phosphorus,  a  practically  inert  substance  which  is 


Am.  Jour.  Pharm. 
June,  1914. 


Progress  in  Pharmacy. 


279 


being  offered  as  a  "  valuable  therapeutic  agent." — /.  Am.  M.  Assoc., 
1914,  vol  62,  pp.  793,  794.    See  also  pp.  1033-1035. 

Argyrism. — Crispin,  Antonio  M.,  reports  a  case  of  argyrism  fol- 
lowing the  use  of  collargol.  The  administration  of  potassium  iodide 
had  not  the  slightest  effect  on  the  resulting  color  of  the  skin.  The 
subsequent  administration  of  hexamethylenamine  caused  the  color  to 
fade  and  become  several  shades  lighter. — /.  Am.  M.  Assoc.]  1914, 
vol.  62,  p.  1394. 

As  pido  spermine.  (Cow,  Douglas.) — Experimental  observations 
on  the  action  of  the  alkaloids  of  quebracho.  Quebrachine  is  by  far 
the  most  toxic  of  the  four  alkaloids  investigated.  In  small  doses 
quebrachine  exerts  a  stimulating  action  on  the  central  nervous  sys- 
tem, as  also  do  the  other  alkaloids.  The  only  obvious  objective  effect 
of  this  is  seen  in  the  respiration,  which  becomes  both  quicker  and 
deeper. — /.  Pharmacol,  and  Exper.  Therap.,  1913-1914,  vol.  5,  pp. 
341-356.  ^ 

Aspirin.  (Reed,  Edward  N.) — Report  of  a  case  of  idiosyncrasy 
to  aspirin  (acetylsalicylic  acid)  in  which  vomiting,  cyanosis,  and 
oedema  followed  the  ingestion  of  5  grains  of  the  drug.  No  treatment 
was  instituted,  and  in  about  six  hours  the  patient  was  comfortable. — 
/.  Am.  M.  Assoc.,  1914,  vol.  62,  p.  773.    See  also  p.  797. 

Creolin  consists  of  the  glycerides  of  fatty  acids  along  with  chol- 
esterins,  lecithin,  and  ethereal  oil,  all  of  which  are  found  in  yeast. 
It  is  prepared  by  extracting  fresh  purified  beer  yeast  with  alcohol 
and  separating  the  dissolved  fat  from  the  alcoholic  extract  by  suit- 
able means.  Creolin  is  said  to  be  useful  in  furunculosis,  acne,  sycosis, 
and  similar  affections  of  the  skin.  It  is  also  said  to  be  useful  in 
habitual  constipation,  leucorrhoea,  erosions  of  the  vagina  and  cervix, 
and  similar  diseases. — -/.  Am.  M.  Assoc.,  1914,  vol.  62,  p.  931. 

Cocaine.  (Editorial.) — The  demand  for  cocaine  for  legitimate 
medicinal  uses  appears  to  have  diminished  considerably  in  recent 
years.  Some  of  the  large  firms,  which  formerly  handled  many  thou- 
sands of  ounces  of  cocaine  in  the  course  of  the  year,  now  do  not  sell 
so  many  hundreds,  while  other  firms  which  also  dealt  in  the  article 
in  not  inconsiderable  quantities  now  sell  practically  none. — Pharm. 
J.,  1914,  vol.  92,  p.  466. 

Collargol.  (Eisendrath,  Daniel  E.) — A  preliminary  note  on  the 
effect  of  injecting  collargol  into  the  renal  pelvis.  The  report  states 
that  death  resulted  in  animals  from  extensive  and  widely-distributed 
collargol  embolism,  and  the  author  believes  that  these  experiments 


28o 


Progress  in  Pharmacy. 


Am.  Jour.  Pharm. 
June,  1914. 


offer  for  the  first  time  a  logical  explanation  of  deaths  observed  in  the 
human  being. — /.  Am.  M.  Assoc.,  igi4,  vol.  62,  pp.  1392,  1393. 

Crotalin. — Anderson,  John  F.,  reports  a  fatal  case  of  bacterial 
infection  from  the  use  of  the  venom  of  Crotalus  horridus  dissolved 
in  water.  He  also  reports  the  examination  of  95  ampoules  of  cro- 
talin solution  prepared  by  four  different  firms,  35  of  which  (38.8 
per  cent.)  were  found  not  to  be  sterile. — /.  Am.  M.  Assoc.,  1914, 
vol.  62,  pp.  893-895. 

Crotalin.  (Yawger,  N.  S.) — Report  on  six  cases  of  epilepsy 
treated  with  crotalin.  Two  patients  were  uninfluenced;  two  were 
worse  during  the  treatment ;  one  early  in  the  course  developed  such 
intolerant  toxic  symptoms  that  further  experimentation  was  unjus- 
tified, and  the  last  patient  died  two  and  a  half  months  after  treatment. 
— /.  Am.  M.  Assoc.,  1914,  vol.  62,  pp.  1533-1535. 

Cymarin. — A  glucoside  obtained  from  Canadian  hemp,  said  to 
have  an  action  on  the  circulation  somewhat  similar  to  digitalis  and 
to  be  an  efficient  diuretic. — Sudd.  Apoth.-Ztg.,  1914,  vol.  54,  p.  62. 

Diachylon.  (Editorial.) — Newcastle-on-Tyne  pharmacists  have 
done  one  of  the  best  things  that  we  have  heard  of  recently,  by  re- 
solving to  stop  the  sale  of  diachylon  plaster  in  the  lump,  or  any  other 
form  which  may  be  taken  internally.  They  have  come  to  this  reso- 
lution after  hearing  from  Mr.  T.  Maltby  Clague  particulars  of  the 
cases  of  lead  poisoning  among  women  due  to  diachylon.  Mr.  Clague 
has  had  excellent  opportunities  in  his  investigations  with  Sir  Thomas 
Oliver,  M.D.,  of  seeing  the  damage  that  is  done  by  diachylon,  and 
he  considers  that  all  self-respecting  registered  chemists  should  refuse 
to  sell  the  stuff  to  anyone.  Its  legitimiate  use  as  a  plaster  is  so  trifling 
nowadays  that  the  public  would  suffer  little  inconvenience  if  they 
could  not  buy  it  from  pharmacies  conducted  under  the  act  of  1908. — 
Chem.  and  Drug.,  1914,  vol.  84,  p.  458. 

Erepton  is  a  product  prepared  by  the  digestion  of  meat  and  con- 
sisting largely  of  amino-acids  thus  produced.  It  is  prepared  by  the 
successive  action  of  pepsin-hydrochloric  acid,  trypsin  and  erepsin 
on  meat  freed  from  fat  and  tendon ;  the  end-product  is  then  desic- 
cated. Erepton  is  a  brownish,  hygroscopic  powder,  easily  soluble 
in  water  and  having  an  odor  and  taste  suggestive  of  meat  extract. — 
/.  Am.  M.  Assoc.,  1914,  vol.  62,  p.  1559. 

Eusitin. — Tablets  containing  the  mucin  substances  obtained  from 
Althcea  rosea  syriens.  Intended  for  use  in  the  treatment  of  obesity, 
the  employment  of  those  tablets  being  based  upon  their  property  of 


Am.  Jour.  Pharm. 
June,  1914. 


Progress  in  Pharmacy. 


281 


abolishing  the  feeling  of  hunger  from  which  patients  suffer  who  are 
placed  on  a  limited  diet. — Chem.  and  Drug.,  1914,  vol.  84,  p.  443. 

Friedmann  Remedy.  (Editorial.) — Several  recent  German 
articles  on  the  Friedmann  remedy  appear  to  be  uniformly  unfavor- 
able. They  add  to  the  testimony  already  given  in  this  country  that  the 
Friedmann  remedy  is  not  inefficient  alone,  but  also  may  be  dangerous. 
All  reliable  reports  regarding  the  treatment  of  patients  by  Fried- 
mann's  method  seem  to  show  either  that  it  is  actually  injurious  or 
else  that  it  is  less  efficient  than  other  well-known  and  less  dangerous 
means  of  treatment. — /.  Am.  M.  Assoc.,  1914,  vol.  62,  p.  1407.  See 
also  pp.  1206  and  1343. 

Hydrogen  Peroxide.  (Stewart,  R.) — There  is  really  a  very  curi- 
ous amount  of  ignorance  prevalent  as  to  hydrogen  peroxide.  The 
ordinary  hydrogen  peroxide  of  commerce  is  now  an  article  sold  by 
the  ton,  and  even  for  many  purposes  of  the  drug  trade  this  quality 
answers  admirably.  The  ordinary  commercial  commodity,  however, 
does  not  compare  in  stability  with  the  higher-priced  product  used 
for  medicinal  purposes.  The  whole  question  is  one  of  price.  So 
long  as  drug  stores,  hospital  authorities,  and  others  expect  a  product 
at  the  very  lowest  possible  price,  it  is  hardly  fair  to  expect  manu- 
facturers to  deliver  goods  which  it  would  cost  two  or  three  times  the 
selling  price  to  produce. — Pharm.  J.,  1914,  vol.  92,  p.  353. 

The  Hypophosphite  Fallacy.  (Anon.) — A  false  therapeutic  no- 
tion born  of  speculation  soon  dies  a  natural  death  if  exposed  unsup- 
ported to  the  cold  world  of  facts,  but  when  nursed  by  commercial 
interests  it  may  be  kept  alive  for  generations.  Interesting  examples 
of  this,  to  name  but  two  or  three,  are  the  misconceptions  perpetuated 
during  the  past  half  century  concerning  "  lithia,"  the  "  natural  " 
salicylates,  and  the  hypophosphites.  In  spite  of  reliably  reported 
observations,  the  hypophosphites  continue  to  be  employed  by  many 
practitioners,  largely  because  the  theory  on  which  their  use  is  based 
was  thought  to  be  plausible  at  the  time  when  chemical  theories  were 
popular  and  gained  a  certain  recognition  and  were  adopted  without 
scientific  investigation.  These  theories  were  subsequently  taken  up' 
by  certain  manufacturers  and  became  a  commercial  asset,  so  that, 
as  a  result,  a  theory  which  uncommercialized  would  have  died  of 
inanition,  was  kept  alive  by  continued  advertisement. — /.  Am.  M. 
Assoc.,  1914,  vol.  62,  pp.  1346,  1347. 

Ipecacuanha.  (Van  der  Wielen  and  Reens.)— An  assay  of  the 
same  sample  of  ipecacuanha  by  the  methods  official  in  the  Pharmaco- 


282 


Progress  in  Pharmacy. 


Am.  Jour.  Pharm. 
June,  1914. 


poeias  named  gave  the  following  wide  variation  in  results :  Japanese 
Pharmacopoeia,  1.78  per  cent. ;  Belgian,  1.71  per  cent. :  United  States, 
1.67  per  cent.;  Swiss,  1.735  Per  cent.;  Swedish,  1.735  Per  cent.; 
Austrian,  2.15  per  cent.;  Hungarian,  2.13  per  cent.;  Dutch,  2.06  per 
cent;  German,  1.54  per  cent.;  Italian,  2.03  per  cent.  These  results 
point  to  the  desirability  of  an  international  process  and  standard. — 
Pharm.  J.,  1914,  vol.  92,  p.  541. 

Leukozon. — Calcium  perborate  mixed  with  talc  and  standardized 
to  a  content  of  5  per  cent,  of  available  oxygen.  Used  as  an  antiseptic 
dusting  powder. — Chem.  and  Drug.,  1914,  vol.  84,  p.  443. 

Liquid  Paraffin. — Peck,  J.  Wicliffe,  in  discussing  the  production 
and  use  of  liquid  paraffin^  says :  "  It  has  been  stated  that  liquid  paraffin 
should  not  be  given  with  meals  or  during  the  process  of  digestion, 
as  it  prevents  the  pancreatic  emulsiflcation  of  fats.  The  experiments 
in  vitro  I  do  not  think  would  be  repeated  in  the  body.  From  prac- 
tical experience,  just  after  a  meal  is  the  time  I  should  suggest.  If 
taken  on  an  empty  stomach  the  oil  passes  through  very  often  un- 
mixed with  the  stools  and  taking  the  usual  thirty  hours.  When 
given  in  excess  to  animals  it  passes  through  with  apparently  no 
colorable  fats  dissolved." — Pharm.  J.,  19 14,  vol.  92,  p.  509. 

Novotryposafrol. — A  derivative  of  tryposafrol,  for  use  in  try- 
panosome  infections  and  also  in  veterinary  medicine. — Chem.  and 
Drug.,  1914,  vol.  84,  p.  443. 

Perydal. — An  antiseptic  dusting  powder,  containing  formalde- 
hyde and  Peruvian  balsam.  It  is  used  as  a  general  antiseptic  for 
wounds,  for  dusting  in  the  stockings,  and  for  infants. — Pharm.  J., 
1914,  vol.  92,  p.  286. 

Phenolphthalein.  (Editorial.) — A  recent  report  of  the  labora- 
tories of  bacteriology  and  physiologic  chemistry  at  the  Jefferson 
Medical  College  in  Philadelphia  states  that  in  twenty  experiments, 
in  each  of  which,  before  beginning  the  trials,  the  subject's  urine 
showed  no  trace  of  albumin  by  delicate  tests,  24-hour-specimen,  col- 
lected after  the  administration  of  phenolphthalein  in  a  from  i-grain 
to  2-grain  dose,  gave  positive  tests  for  protein  in  every  case.  *The 
amount  of  albumin  varied  from  a  trace  up  to  0.25  per  cent,  by 
Esbach's  quantitative  method.  The  precipitate  in  many  of  the  cases 
was  tested  and  found  to  be  insoluble  in  alcohol.  Traces  of  phenol- 
phthalein were  demonstrated  in  the  urine.  The  albuminuria  lasted 
from  one  to  three  days. — /.  Am.  M.  Assoc.,  1914,  vol.  62,  p.  1560. 

Phenolphthalein-agar  is  agar-agar  impregnated  with  phenolph- 
thalein, 100  Gm.  containing  3  Gm.  of  phenolphthalein.  Phenolphtha- 


Am.  Jour.  Pharm. 
June,  1914. 


Progress  in  Pharmacy. 


283 


lein-agar  is  prepared  by  impregnating  1000  Gm.  of  agar-agar  with  a 
solution  obtained  by  dissolving  30  Gm.  of  phenolphthalein  in  a  mix- 
ture of  2000  Cc.  of  water  and  700  Cc.  of  alcohol  and  drying  the 
impregnated  agar-agar  slowly. — /.  Am.  M.  Assoc.,  1914,  vol.  62, 
p.  1 168. 

Quinine  Poisoning.  (Underhill,  Elizabeth  C.) — Report  of  a  case 
of  quinine  poisoning  in  a  woman,  age  20,  who  took  at  one  dose  100 
2-grain  quinine  pills.  The  toxic  symptoms  were  accompanied  by 
impairment  of  vision,  which  improved  gradually. — /.  Am.  M.  Assoc., 
1914,  vol.  62,  pp.  1396,  1397.    See  also  p.  920. 

Quinine-urea  Hydrochloride.  (Abstract.) — There  is  a  certain 
element  of  danger  attending  the  use  of  quinine-urea  hydrochloride  as 
a  local  anaesthetic.  It  has  been  pointed  out  that  sloughing  may  follow 
its  use  when  a  solution  stronger  than  3  per  cent,  is  used.  An  exten- 
sive abscess  has  followed  the  use  of  a  1  per  cent,  solution  for  the 
removal  of  internal  hemorrhoids,  and  two  cases  of  sloughing  follow- 
ing the  use  of  a  2  per  cent,  solution  in  similar  operations  are  re- 
corded. The  general  opinion  is  that  solutions  of  this  substance  should 
not  be  stronger  than  1  per  cent. ;  some  observers  recommend  even 
weaker  solutions,  and  with  proper  attention  to  technic  bad  effects 
may  be  greatly  reduced. — Pharm.  J.,  1914,  vol.  92,  p.  368. 

Riopan. — A  concentrated  preparation  of  ipecacuanha  sent  out 
as  a  brownish  powder,  soluble  in  water.  It  is  standardized  to  con- 
tain 50  per  cent,  of  ipecacuanha  alkaloids  in  the  form  of  their  hydro- 
chlorides; the  other  more  or  less  inert  substances  are  also  present. 
One  part  of  riopan  is  equivalent  to  20  parts  of  ipecacuanha  root. — 
Chem.  and  Drug.,  1914,  vol.  84,  p.  443. 

Salvarsan. — No  one  can  dispute  the  statement  that  many  of  the 
deaths  from  salvarsan  have  been  caused  by  its  ill-considered  use, 
either  in  the  face  of  contra-indications  or  in  too  large  or  too  fre- 
quent dosage,  but  to  argue  from  this  that  the  fatalities  are  therefore 
not  due  to  salvarsan  and  that  salvarsan  is  not  toxic  is  far  from 
logical.  The  unwise  use  of  salvarsan  may  be  expected  as  a  result  of 
such  arguments,  and  the  stubborn  denial  of  the  toxicity  of  the  drug 
has  encouraged  its  careless  administration. — /.  Am.  M.  Assoc.,  1914, 
vol.  62,  p.  1 176. 

Neosalvarsan.  (Anon.) — Seven  deaths  have  occurred  in  the  Los 
Angeles  Hospital  within  two  days  following  intraspinal  injections 
of  a  solution  of  neosalvarsan  in  autogenous  serum,  and  another 
patient  is  reported  as  being  likely  to  die. — /.  Am.  M.  Assoc.,  1914, 
vol.  62,  pp.  861,  862.   See  also  pp.  957,  958. 


284 


Progress  in  Pharmacy. 


Am.  Jour.  Pharm. 
June,  1914. 


Sarsaparilla.  (Editorial.) — The  proposition  to  include  in  the 
Pharmacopoeia  of  the  United  States,  Mexican,  Honduras,  Para,  and 
Jamaica  varieties  of  sarsaparilla  is  especially  interesting  in  connec- 
tion with  the  revision  of  the  British  Pharmocopceia,  it  being  under- 
stood that  this  good  old-fashioned  drug  does  not  commend  itself 
to  the  Oxford  Street  savants,  who  desire  to  relegate  it  to  the  limbo 
of  ex-official  things. — Chem.  and  Drug.,  1914,  vol.  84,  p.  566. 

Serum  Treatment  of  Tetanus.  (Editorial.) — The  great  value  of 
antitetanus  serum  as  a  preventive  is  unquestioned.  As  a  specific 
cure,  however,  this  serum  has  fallen  far  short  of  the  earliest  expec- 
tations ;  it  even  has  been  asserted  that  so  far  the  statistics  and  the 
evidence  obtained  from  watching  patients  treated  with  serum  do  not 
indicate  that  it  has  any  real  curative  value.  It  has  been  shown  ex- 
perimentally, however,  that  antitetanus  serum  may  save  animals 
already  suffering  from  the  symptoms  of  an  otherwise  fatal  intoxi- 
cation, but  in  order  to  accomplish  this  result  the  serum  must  be  given 
in  several  hundred  times  the  quantity  required  merely  to  protect,  and 
it  must  be  injected  within  a  short  time,  from  24  to  36  hours,  after 
the  onset  of  the  tetanus.  Furthermore,  it  cannot  be  denied  that  the 
weight  of  statistics  favors  the  serum. — /.  Am.  M.  Assoc.,  1914,  vol. 
62,  pp.  1 174,  1 175. 

Silver  Methylene  Blue  contains  24  per  cent,  of  silver.  Is  being 
tried  as  an  antiseptic,  as  it  is  assumed  to  possess  a  powerful  bacteri- 
cidal action  in  various  infectious  processes. — Chem.  and  Drug.,  1914, 
vol.  84,  p.  443. 

Tenosin. — The  active  constituents  of  ergot  are  now  contracted 
to  three  substances,  ^-oxyphenolethylamine,  beta-imidazolylethylam- 
ine,  and  ergotoxin.  For  therapeutic  purposes  only  the  first  two 
substances  come  into  consideration,  as  the  ergotoxin  is  the  gengren- 
producing  substance  of  ergot.  Tenosin  is  said  to  be  a  mixture  of  the 
two  amines  mentioned  above,  and  is  available  either  in  the  form  of 
ampoules  or  as  a  liquid  for  internal  administration. — Sildd.  Apoth- 
Ztg.,  1914,  vol.  54,  p.  63. 

Theobromine  Sodium,  Salicylate.  (Puckner  and  Leach.) — Report 
of  an  investigation  of  the  available  brands  of  theobromine  sodium 
salicylate.  The  results  of  the  investigation,  which  are  in  the  form  of 
a  table,  show  some  variation  in  the  moisture  content  and  also  in  the 
actual  theobromine  content  of  the  dried  specimens;  the  variation  is 
unimportant.  .The  products  in  their  original  state  (undried),  as 
compared  in  relation  to  the  theobromine  content  (the  highest  per- 


Am.  Jour.  Pharm. 
June,  1914. 


Amendment  to  Regulation  p. 


285 


centage  of  theobromine  being  48.61,  the  lowest  45.24),  reveal  a 
variation  of  only  about  3  per  cent.,  a  variation  which  is  negligible  in 
the  case  of  such  drugs  as  theobromine. — /.  Am.  M.  Assoc.,  1914, 
vol.  62,  pp.  1 108,  1 109. 

Tobacco  Snuff.  (Anon.) — The  Supreme  Court  of  North  Dakota 
holds  constitutional  the  antisnuff  act  of  that  State  of  1913,  which 
makes  it  unlawful  to  import,  manufacture,  distribute,  or  give  away 
snuff,  or  substitute  therefor,  under  whatever  name  called. — /.  Am. 
M.  Assoc.,  1914,  vol.  62,  p.  1424. 

Tricarbin. — Under  this  name,  or  as  glycarbin,  glyceryl  carbonate 
has  been  introduced  as  a  chemical  inert  diluent  and  basis  for  medici- 
nal substances  and  galenical  preparations  such  as  pills,  powders, 
tablets,  and  cosmetic  preparations.  It  occurs  as  a  crystalline  non- 
hygroscopic,  permanent,  insoluble  powder ;  it  melts  with  decomposi- 
tion at  about  1490  C. — Pharm.  J.,  1914,  vol.  92,  p.  286. 

Vitamines.  (Anon.) — Vitamine  is  the  name  given  to  a  substance 
which  is  believed  to  be  necessary  to  prevent  the  nervous  lesions 
characteristic  of  beriberi.  It  is  regarded  as  an  antineuritic  agent 
naturally  present  in  rice,  the  removal  of  which  by  polishing  causes 
the  symptoms  of  the  disease  to  appear.  The  name  appears  to  be  de- 
rived from  vita  (life  and  amine),  indicating  its  chemical  character. 
The  substance  was  at  first  thought  to  be  a  pyrimidine  base  with  the 
following  formula  :  C17H20O7N2.  It  was  at  first  believed  to  have  the 
constitution  of  a  ureide,  but  in  his  latest  work  Funk  states  that  the 
nitrogen  is  not  present  in  the  amino  form.  Vitamine  was  first  found 
in  rice  and  was  connected  with  beriberi.  Other  substances  of  similar 
character  were  subsequently  discovered,  and  the  name  has  become 
descriptive  of  a  class.  Vitamine  was  discovered  in  191 2  by  Casimir 
Funk. — /.  Am.  M.  Assoc.,  19 14,  vol.  62,  p.  1349. 


CORRESPONDENCE. 

Amendment  to  Regulation  9,  Relating  to  Guaranties  by  Wholesalers, 
Jobbers,  Manufacturers,  and  Other  Parties  Residing  in  the 
United  States  to  Protect  Dealers  from  Prosecution. 

Regulation  9  of  the  Rules  and  Regulations  for  the  enforcement  of 
the  Food  and  Drugs  Act,  June  30,  1906  (34  Stat.,  768),  United 
States  Department  of  Agriculture,  is  hereby  amended,  effective  May 
1,  1915,  so  as  to  read  as  follows: 


286 


Amendment  to  Regulation  p. 


f  Am.  Jour.  Pharm. 
\      June,  1914. 


REGULATION  9.  GUARANTY. 

(Section  9.) 

(a)  It  having  been  determined  that  the  legends  "  Guaranteed 
under  the  Food  and  Drugs  Act,  June  30,  1906,"  and  "  Guaranteed 
by  (name  of  guarantor),  under  the  Food  and  Drugs  Act,  June  30, 
1906,"  borne  on  the  labels  or  packages  of  food  and  drugs,  accom- 
panied by  serial  numbers  given  by  the  Secretary  of  Agriculture,  are 
each  misleading  and  deceptive,  in  that  the  public  is  induced  by  such 
legends  and  serial  numbers  to  believe  that  the  articles  to  which  they 
relate  have  been  examined  and  approved  by  the  Government  and 
that  the  Government  guarantees  that  they  comply  with  the  law,  the 
use  of  either  legend,  or  any  similar  legend,  on  labels  or  packages 
should  be  discontinued.  Inasmuch  as  the  acceptance  by  the  Sec- 
retary of  Agriculture  for  filing  of  the  guaranties  of  manufacturers 
and  dealers  and  the  giving  by  him  of  serial  numbers  thereto  con- 
tribute to  the  deceptive  character  of  legends  on  labels  and  packages, 
no  guaranty  in  any  form  shall  hereafter  be  filed  with  and  no  serial 
number  shall  hereafter  be  given  to  any  guaranty  by  the  Secretary 
of  Agriculture.  All  guaranties  now  on  file  with  the  Secretary  of 
Agriculture  shall  be  stricken  from  the  files,  and  the  serial  numbers 
assigned  to  such  guaranties  shall  be  canceled. 

( b)  The  use  on  the  label  or  package  of  any  food  or  drug  of  any 
serial  number  required  to  be  canceled  by  paragraph  (a)  of  this 
regulation  is  prohibited. 

(c)  Any  wholesaler,  manufacturer,  jobber,  or  other  party  resid- 
ing in  the  United  States  may  furnish  to  any  dealer  to  whom  he  sells 
any  article  of  food  or  drug  a  guaranty  that  such  article  is  not  adul- 
terated or  misbranded  within  the  meaning  of  the  Food  and  Drugs 
Act,  June  30,  1906,  as  amended. 

(d)  Each  guaranty  to  afford  protection  shall  be  signed  by,  and 
shall  contain  the  name  and  address  of,  the  wholesaler,  manufacturer, 
jobber,  dealer,  or  other  party  residing  in  the  United  States  making 
the  sale  of  the  article  or  articles  covered  by  it  to  the  dealer,  and  shall 
be  to  the  effect  that  such  article  or  articles  are  not  adulterated  or 
misbranded  within  the  meaning  of  the  Federal  Food  and  Drugs  Act. 

(e)  Each  guaranty  in  respect  to  any  article  or  articles  should  be 
incorporated  in  or  attached  to  the  bill  of  sale,  invoice,  bill  of  lading, 
or  other  schedule,  giving  the  names  and  quantities  of  the  article  or 
articles  sold,  and  should  not  appear  on  the  labels  or  packages. 


Am.  Jour.  Pharm. ) 
June,  1914.  / 


Abolition  of  Legend  Postponed. 


287 


(/)  No  dealer  in  food  or  drug  products  will  be  liable  to  prosecu- 
tion if  he  can  establish  that  the  articles  were  sold  under  a  guaranty 
given  in  compliance  with  this  regulation. 

W.  G.  McAdoo, 

Secretary  of  the  Treasury. 
D.  F.  Houston, 

Secretary  of  Agriculture. 
William  C.  Redfield, 
Secretary  of  Commerce. 

Washington,  D.  C,  May,  5,  1914. 


ABOLITION  OF  GUARANTY  LEGEND  POSTPONED. 

Revised  Food  Inspection  Decision  Allows  Manufacturers  Additional 
Year  in  Which  to  Exhaust  Stock  of  Labels. 

Washington,  D.  C,  May  29,  19 14.  It  was  announced  to-day  that 
it  had  been  decided  to  postpone  the  effective  date  of  Food  Inspection 
Decision  153,  which,  in  substance,  abolishes,  after  May  1,  19 15,  the 
present  guaranty  legend  on  food  and  drugs. 

This  legend,  now  in  general  use  by  manufacturers,  is  "  Guar- 
anteed by  (name  of  guarantor)  under  the  Food  and  Drugs  Act." 
The  Secretaries  of  the  Treasury,  Agriculture,  and  Commerce  have 
found  it  to  be  misleading  and  deceptive.  Many  people  have  been 
induced  to  believe  that  all  articles  labelled  with  the  legend  have  been 
examined  and  approved  by  the  Government.  The  facts  are  that 
putting  the  legend  on  labels  by  manufacturers  is  entirely  voluntary, 
and  that  the  Government  never  guarantees  the  wholesomeness  or 
purity  of  food  or  drug  products. 

It  appears  that,  acting  in  accordance  with  the  regulation  now  in 
force,  which  permits  the  legend,  many  manufacturers  have  supplied 
themselves  with  large  stocks  of  labels  which  cannot  be  used  up  by 
May  1,  191 5.  The  result  is  that  if  the  regulation,  as  amended  by 
Food  Inspection  Decision  153,  should  go  into  effect  May  1,  191 5, 
large  losses  would  accrue  to  citizens  who  have  expended  their  money 
for  labels  in  good  faith  and  in  an  effort  to  comply  with  existing 
regulations. 

To  meet  this  situation  the  effective  date  of  the  amendment  to  the 
regulation  will  be  postponed  until  May  1,  1916,  and  as  to  products 
packed  and  labelled  prior  to  May  1,  191 6,  in  compliance  with  law  and 
with  the  present  regulations,  it  will  be  postponed  until  November  r, 


288  Constituents  of  Senna.  { 


Am.  Jour.  Pharm. 
June.  1914. 


1 916.    Meanwhile,  manufacturers  may,  and  doubtless  many  will, 
label  their  good  in  compliance  with  the  new  regulations. 
The  decision  is  as  follows: 

FOOD  INSPECTION  DECISION  NO.  1 55. 

Changing  Effective  Date  of  Food  Inspection  Decision  No.  15J, 
which  Amends  Regulation  9,  Relating  to  Guaranties  by  Whole- 
salers, Jobbers,  Manufacturers,  and  other  Parties  Residing  in 
the  United  States  to  Protect  Dealers  from  Prosecution. 
The  effective  date  of  Food  Inspection  Decision  No.  153,  issued 
May  5,  1914,  is  hereby  postponed  until  May  1,  1916;  Provided,  That 
as  to  products  packed  and  labelled  prior  to  May  1,  1916,  in  accordance 
with  law  and  with  the  regulations  in  force  prior  to  May  5,  19 14,  it 
shall  become  effective  November  1,  1916;  And  Provided  Further, 
That  compliance  with  the  terms  of  Regulation  9  of  the  Rules  and 
Regulations  for  the  Enforcement  of  the  Food  and  Drugs  Act  as 
amended  by  Food  Inspection  Decision  No.  153  will  be  permitted  at 
any  time  after  the  date  of  this  decision. 

C.  S.  Hamlin, 
Acting  Secretary  of  the  Treasury. 

D.  F.  Houston, 
Secretary  of  Agriculture. 

Wm.  C.  Redfield, 
Secretary  of  Commerce. 

Washington,  D.  C,  May  29,  1914. 


CURRENT  LITERATURE. 

Constituents  of  Senna. 

An  investigation  of  senna  leaves  to  determine  the  exact  constit- 
uents present  revealed  many  interesting  things  about  this  well-known 
drug. 

Tinnevelly  senna  leaves  (Cassia  angustifolia,  Vahl)  ;  senna  leaves 
from  Lima,  Peru,  which  were  found  to  be  botanically  identical  with 
the  Tinnevelly  leaves,  and  Alexandrian  senna  leaves  were  used. 

An  alcoholic  extract  of  the  Tinnevelly  leaves,  when  distilled  with 
steam,  yielded  a  small  amount  of  an  essential  oil.  From  the  portion 
of  the  extract  which  was  soluble  in  water  the  following  substances 
were  isolated  :  Salicylic  acid,  rhein,  C15H8Oe ;  kaempferol,  C15H10O6 ; 
aloe-emodin,  C15H10O5 ;  kaempferin,  C27H30O16,  6  H20  (m.  p.  1850- 
1950),  a  new  glucoside  of  kaempferol;  a  mixture  of  the  glucosides 


Am'j^ner'i£4arm*}  Constituents  of  Senna,  289 

of  rhein  and  aloe-emodin ;  the  magnesium  salt  of  an  unidentified 
organic  acid.  The  aqueous  liquid  furthermore  contained  a  quantity 
of  a  sugar  which  yielded  d-phenylglucosazone  (m.  p.  2160),  and  some 
brown,  amorphous  products,  which,  on  treatment  with  alkali,  gave 
kaempferol,  together  with  small  amounts  of  rhein  and  aloe-emodin. 
Some  amorphous,  glucoside  material  was  also  present. 

The  portion  of  the  alcoholic  extract  which  was  insoluble  in  water 
consisted  of  a  soft,  dark  green  resin,  which  amounted  to  7.0  per 
cent,  of  the  weight  of  the  leaves  employed.  From  this  material, 
which  contained  considerable  chlorophyll  and  amorphous  products, 
there  were  isolated,  in  addition  to  some  of  the  substances  mentioned 
above,  the  following  compounds :  Myricyl  alcohol ;  a  phytosterol, 
C27H4eO ;  a  phytosterolin,  C33H5606 ;  palmitic  and  stearic  acids. 

The  senna  leaves  from  Lima,  Peru,  were  found  to  contain  all 
the  above-mentioned  compounds,  with  the  exception  of  the  magne- 
sium salt,  and,  in  addition,  worhamnetin.  A  glucoside  of  worhamne- 
tin  was  also  present  in  association  with  glucosides  of  kaempferol, 
rhein,  and  aloe-emodin,  but  no  pure  compound  could  be  isolated  from 
the  mixture. 

Alexandrian  senna  leaves  yielded,  in  addition  to  myricyl  alcohol 
and  a  phytosterolin,  rhein,  aloe-emodin,  kaempferol,  and  worhamne- 
tin.  These  four  substances  were  also  present  in  the  form  of  gluco- 
sides, and  in  much  greater  proportion  as  such  than  in  the  free  state. 

The  statements  of  Tschirch  and  Hiepe  (Arch.  Pharm.,  1900, 
238,  427)  that  senna  leaves  contain  "  sennawoemodin,"  "  senna- 
chrysophanic  acid"  (chrysophanol),  and  a  "substance,  C14H10O5," 
could  not  be  confirmed,  it  having  been  ascertained  that  the  anthra- 
quinone  derivatives  present  consist  solely  of  rhein  and  aloe-emodin. 
In  this  connection  it  may  be  noted  that  a  mixture  of  approximately 
equal  quantities  of  the  last-mentioned  two  compounds  has  the  em- 
pirical composition  and  properties  assigned  by  Tschirch  and  Hiepe 
to  the  "  substance  C14H10O5."  Furthermore,  the  "  sennarhamne- 
tin  "  of  the  last-mentioned  authors  has  been  found  to  be  identical 
with  the  uorhamnetin  previously  described  by  Perkin  (T.,  1896,  69, 

1658). 

Frank  Tutin,  from  the  Transactions  of  the  Chemical  Society, 
vol.  103,  1913.   London.  J.  K.  T. 

The  Serum  Treatment  of  Hay  Fever. — In  a  pamphlet,  by 
Lewis  M.  Somers,  M.D.,  published  by  Fritzsche  Brothers,  New 
York,  a  summary  of  ten  years'  experience  in  the  use  of  pollen 


290 


The  U.  S.  Pharmacopoeia. 


Am.  Jour.  Pharm. 
June,  1914. 


antitoxines,  Dr.  Somers  demonstrates  that  from  the  very  nature 
of  the  disease  no  single  therapeutic  agent  can  act  as  a  specific,  nor 
even  modify  the  symptoms  in  every  case.  The  serum  formerly  used 
was  prepared  by  the  action  of  the  pollen  toxin  of  either  spring  or 
fall  plants  upon  the  horse,  and  the  resulting  serum  bodies  being 
the  therapeutic  agent  employed.  Many  experiments  with  the  pollen 
toxin  upon  individuals  subject  to  hay  fever  have  shown  that  in 
dilutions  of  one  in  ten  thousand,  when  placed  in  the  eyes  or  nose, 
typical  attacks  of  hay  fever  have  been  produced,  in  which  the 
symptoms  are  as  irregular  and  peculiar  as  in  a  natural  attack.  The 
use  of  the  antitoxin  in  these  artificial  cases  promptly  checks  the 
symptoms  and  causes  the  attack  to  disappear.  In  the  case  of  in- 
dividuals not  subject  to  hay  fever  the  toxin  had  no  effect  whatever. 
An  antitoxin  has  been  prepared  by  Dunbar,  combining  pollen  from 
spring  plants  and  fall  grasses,  and  has  been  experimented  with  with 
satisfactory  results.  Summarizing  the  experience  of  ten  years'  use 
of  pollen  antitoxin,  the  following  conclusions  were  reached:  "  1. 
The  serum  produces  prompt  and  positive  amelioration  of  the  symp- 
toms of  hay  fever  in  the  majority  of  cases.  2.  In  a  smaller  number 
this  is  accompanied  with  complete  disappearance  of  the  affection  for 
that  particular  season.  3.  When  results  are  obtained,  it  favorably 
influences  all  the  manifestations  of  hay  fever  in  the  larger  number 
of  cases,  while  in  a  smaller  class  one  or  more  of  the  symptoms  seem 
to  be  most  markedly  influenced.  4.  When  given  during  the  attack 
of  hay  fever,  irrespective  of  its  severity,  it  produces  palliation  rather 
than  absolute  cure.  5.  When  successfully  used  during  one  season, 
it  does  not  prevent  the  reappearance  of  the  disease  the  following 
season,  although  there  is  reason  to  believe  that  a  slight  influence  in 
modifying  further  attacks  does  exist." 

Philip  F.  Fackenthall. 


THE  U  S.  PHARMACOPOEIA  IX. 

Prof.  Joseph  P.  Remington,  chairman  of  the  Committee  of  Re- 
vision, in  a  recent  address  before  the  New  York  Branch  of  the 
A.  Ph.  A.,  stated  that  the  work  of  revision  was  fast  approaching  com- 
pletion and  that  the  book  would  soon  be  printed.  By  international 
agreement  it  will  contain  the  same  strength  and  doses  for  all  power- 
ful preparations  as  do  many  of  the  leading  pharmacopoeias  of  the 
world.   Tentatively,  there  will  be  798  articles  in  the  new  U.  S1.  P. 


THE  AMEEIOAN 


JOURNAL  OF  P  H ASKMA 0 Y 


From  the  Division  of  Pharmacology,  Leland  Stanford  Jr.  University. 

After  having  discovered  the  pressor  action  of  the  extracts  of  the 
adrenal  glands,  Oliver  and  Schaefer  1  studied  the  action  of  those 
made  from  other  ductless  glands.  They  found  that  aqueous  or 
glycerine  extracts  of  sheep  pituitaries,  on  intravenous  injection  into 
certain  animals,  caused  a  persistent  rise  in  blood-pressure,  usually, 
but  not  always,  associated  with  a  slowed  heart-rate.  This  rise  oc- 
curred even  in  animals  with  the  medulla  destroyed,  and  perfusion 
experiments  proved  the  action  to  be  mainly  peripheral.  An  increase 
in  the  force  of  the  heart  action  is  partly  responsible  for  this  rise, 
as  extracts  of  pituitary  glands  act  directly  on  the  muscle-fibres  of 
the  vessels  and  heart.  The  pressor  action  is  especially  marked  in 
cases  of  artificially  lowered  blood-pressure. 

The  few  experiments  which  Szymonowicz  2  made  suggested  that 
extracts  of  this  organ  caused  a  fall  in  blood-pressure  with  a  rapid 
heart-beat,  the  opposite  condition  to  what  Oliver  and  Schaefer 
found.  Silvestrini 3  merely  noted  a  fall  in  blood-pressure,  and  this 
seemed  to  be  the  characteristic  reaction.  According  to  von  Cyon, 
there  are  two  compounds :  one  which  slows  and  strengthens  the 

1  Oliver,  G.,  and  Schaefer,  E.  A.,  "  On  the  Physiological  Action  of  Ex- 
tracts of' Pituitary  Body,"  Jour,  of  Physiology,  vol.  18,  p.  277  (1895). 

2  Szymonowicz,  L.,  "  Die  Function  der  Nebennieren,"  Archiv.  f.  Physiol, 
vol.  64,  p.  131  (1896). 

3  Silvestrini,  R.,  "  Sull'  azione  dell'  estratto  aquoso  del  lobo  posteriore  dell' 
ipofisi  sulla  pressione  sanguinea,"  Rcvista  critica  di  din.  mcd.,  No.  28,  1905, 
seen  only  in  reference. 


CONTRIBUTION  TO  THE  CHE^&|^Y  ^\%HE 
PITUITARY  PRESSOR  COMPtTTO^>5^' 


By  Albert  C.  Crawford  and  Zeno  Ostenberg, 


1291) 


292 


Chemistry  of  Pressor  Compounds.     {Am  j°™' ilurm" 


heart,  while  the  other  causes  a  rise  in  blood-pressure  through  inhi- 
bition of  the  depressor  nerve.4 

Howell 0  traced  the  pressor  action  of  the  pituitary  exclusively  to 
the  infundibular  portion,  and  found  that,  if  the  injection  of  extracts 
of  this  portion  were  repeated  rapidly,  the  second  injection  caused 
no  rise  in  blood-pressure  and  produced  no  cardiac  inhibition.  He 
also  found  that  extracts  of  the  anterior  lobe  usually  induced  no 
effect,  either  on  the  blood-pressure  or  on  the  heart- rate.  If  the 
vagi  were  intact,  as  in  Oliver  and  Schaefer's  original  experiments, 
extracts  of  the  infundibular  lobe  caused  a  rise  in  blood-pressure 
with  a  slow  heart-beat,  but  if  the  vagi  were  cut  there  was  a  rise  in 
pressure  with  less  slowing  than  when  the  vagi  were  intact,  hence  the 
action  is  partly  central.  Other  workers  have  found  that  some  of 
the  cardiac  slowing  is  peripheral  in  origin.6 

In  Howell's  experiments  both  sheep  and  dog  pituitaries  were 
used  and  were  tested  on  dogs.  Schaefer  and  Vincent 7  confirmed 
Howell's  conclusions  that  the  pressor  principle  was  confined  to  the 
infundibular  portion,  and  the  latter  workers  made  the  further  sug- 
gestion that  in  extracts  of  this  gland  there  was  a  depressor  com- 
pound. They  agreed  with  Howell  that  a  second  injection,  if  given 
too  soon  after  the  first,  would  cause  no  immediate  rise  in  blood- 
pressure,  but  claimed  there  might  be  a  delayed  rise  and  that  the 
second  injection  produced  a  more  marked  fall,  so  that  no  tolerance 
to  the  depressor  action  was  produced.  The  depressor  action  still 
occurred  after  the  use  of  atropin  and  was,  therefore,  not  due  to 
cholin.  Slowing  of  the  heart  was  not  constant,  but  when  present 
might  be  very  persistent. 

They  found  that  the  pressor  compound,  at  least  in  the  form  in 
which  it  existed  in  the  glands,  was  insoluble  in  alcohol  or  ether, 
while  the  depressor  body  was  soluble  in  absolute  alcohol.  Schaefer 

4  Cyon,  E.  v.,  "  Die  physiologischen  Herzgiften,"  Arch.  f.  ges.  Physiol., 
vol.  73,  p.  339  (1898). 

5  Howell,  W.  H.,  "  Physiological  Effects  of  Extracts  of  the  Hypophysis," 
Jour.  Exper.  Med.,  vol.  3,  p.  245  (1898). 

6  Hebdom,  K.,  "  Ueber  die  Einwirkung  verschiedener  Stoffe  auf  das 
isolierter  Saugetierherz,"  Skan.  Arch.  /.  Physiol.,  vol.  8,  p.  147  (1898)  ;  Cleg- 
horn,  A.,  "  Action  of  Animal  Extracts  ...  on  Mammalian  Heart 
Muscle,"  Amer.  Jour.  Physiol.,  vol.  2,  p.  273  (1899). 

7  Schaefer,  E.,  and  Vincent,  S.,  "  Physiological  Effects  of  Extracts  of  the 
Pituitary  Body,"  Jour.  Physiol.,  vol.  25,  p.  87  (1899). 


Am* ju?yr"iS.4arm* }    Chemistry  of  Pressor  Compounds.  293 

and  Herring  8  found  little  or  no  rise  in  blood-pressure  if  the  pitui- 
tary extracts  were  given  animals  by  mouth,  but  believed  the  com- 
pound which  gave  immunity  was  still  absorbed,  because  the  depressor 
effect  of  intravenous  injections  was  more  marked  if  given  after  the 
oral  use  of  such  extracts.  They  state  that  a  very  small  dose  ( 1  c.c. 
of  a  1  per  cent,  extract)  does  not  produce  immunity,  although  the 
rise  in  blood-pressure  which  follows  a  second  injection  is  less  than 
that  which  follows  the  first.  In  this  connection  it  is  interesting  to 
note  that  Biedl 9  and  also  Cushing  have  found  that  removal  of  the 
posterior  lobe  is  borne  by  dogs  apparently  with  slight  danger  to 
life,  whereas  removal  of  the  anterior  lobe  will  cause  death  within 
a  few  days;  also  Ott  and  Scott 10  have  found  that  the  injection  of 
extracts  of  the  posterior  lobe  will  cause  a  diminution  in  size  of  the 
thyreoid  gland,  but  that  extracts  of  the  anterior  lobe  will  cause 
enlargement  of  this  gland. 

In  Hamburger's  experiments  extracts  of  the  anterior  lobe  caused 
a  fall  in  blood-pressure  with  weakening  of  the  heart  and  accelera- 
tion of  the  rate,  while  a  second  injection,  if  given  early,  produced 
no  effect  on  the  blood-pressure,  although  if  the  interval  between 
injections  was  longer  a  fall  still  occurred.  At  the  autopsy  of  one  of 
Biedl's  animals,  similarly  injected,  there  was  widespread  clotting.11 

The  fall  from  injection  of  extracts  of  the  anterior  lobe  is  more 
marked  in  atropinized  animals,  but  Biedl 12  does  not  consider  the 
fall  produced  by  extracts  of  the  anterior  lobe  as  characteristic. 
Hamburger  noted  that  a  secondary  rise  at  times  followed  the  depres- 
sion caused  by  the  injection  of  extracts  of  the  anterior  lobe.13 

fknile-Weil  and  Boye  14  claim  there  is  a  further  difference  be- 
tween the  action  of  extracts  of  the  anterior  and  of  the  posterior 


8  Shaefer,  E.,  and  Herring,  P.  T.,  "  Action  of  Pituitary  Extracts  upon  the 
Kidney,"  Philos.  Trans.  Roy.  Soc.  London,  Ser.  B,  vol.  199,  p.  1  (1908). 

9  Biedl,  A.,  "  Innere  Sekretion,"  vol.  2,  p.  116. 

10  Ott,  I.,  and  Scott,  J.  C,  "  Effect  of  Animal  Extracts  and  Iodine  upon 
the  Volume  of  the  Thyroid  Gland,"  Thcrap.  Gaz.,  vol.  37,  p.  781  (1913). 

11  Biedl,  /.  c,  p.  141. 

12  Biedl,  /.  c,  p.  141. 

13  Hamburger,  W.  W.,  "Action  of  Intravenous  Injections  of  Glandular 
Extracts,"  Amer.  Jour.  Physiol.,  vol.  11,  p.  282  (1904). 

14  £mile-Weil,  P.,  and  Boye,  G.,  "  Action  differente  des  lobes  hypophy- 
saires  sur  la  coagulation  du  sang,"  Compt.  rend.  Hcb.  Soc.  dc  Biol.,  vol.  67, 
p.  428  (1909). 


294  Chemistry  of  Pressor  Compounds.     { Am' fuiuyr*  m* 

lobes,  in  that  extracts  of  the  latter  favor  coagulation  of  the  blood, 
while  those  of  the  former  do  not. 

Paton  and  Watson15  have  found  that  extracts  of  the  pituitary 
gland  (pituitrin),  when  injected  intravenously  into  birds,  caused  a 
fall  in  blood-pressure,  and  that  after  repeated  injections  this  de- 
pressor action  failed  to  appear,  although,  at  times,  .such  injections 
caused  a  rise  in  blood-pressure.  In  birds  the  fall  in  pressure  was 
due  to  dilatation  of  the  abdominal  vessels,  and  might  be  neutralized 
by  more  powerful  ventricular  contraction. 

It  has  been  recently  shown  that  the  effects  of  extracts  of  the 
pituitary  gland  depend  to  some  extent  upon  how  rapidly  they  are  in- 
jected; thus  Miller  and  Miller  10  state  that  "  if  a  strong  saline  ex- 
tract of  the  posterior  lobe  of  the  hypophysis  be  injected  rapidly  a 
depressor  effect  only  may  be  obtained,  whilst  if  the  injection  be 
made  slowly  or  in  a  very  dilute  form,  the  pressor  effect  predomi- 
nates." 

On  purely  histological  evidence  Herring  17  separated  the  pituitary 
gland  into  an  anterior,  a  posterior,  and  an  intermediary  portion,  and 
argued  that  the  pressor  principle  originated  in  the  pars  intermedia. 
Recently  Lewis,  Miller  and  Matthews  18  have  found  that  the  more 
sharply  the  intermediary  portion  of  the  pituitary  is  removed  and 
extracted,  the  greater  the  rise  in  blood-pressure  which  results  from 
injection  of  such  extracts,  and  the  less  of  the  pars  intermedia  is 
used  the  less  the  rise.  Biedl  claims  that  the  pars  intermedia  can  be 
removed  comparatively  easily  in  thyreoidectomized  animals  and  that 
the  injection  of  aqueous  extracts  of  this  portion  of  the  gland  causes 
a  slowed  heart  with  a  rise  in  blood-pressure,  while  extracts  of  the 
pars  nervosa,  freed  from  the  pars  intermedia,  are  inactive,  save  in 
producing  a  slight  fall. 

15  Paton,  D.  H.,  and  Watson,  A.,  "  Actions  of  Pituitrin,  Adrenalin,  and 
Barium  on  the  Circulation  of  the  Bird,"  Jour  of  Physiol,  vol.  44,  p.  413  (1912). 

16  Miller,  J.  L.,  and  Miller,  E.  M.,  "  Effects  on  Blood-pressure  of  Organ 
Extracts,"  Jour,  of  Physiol.,  vol.  43,  p.  242  (1911). 

17  Herring,  P.  T.,  "  Histological  Appearances  of  the  Mammalian  Pituitary 
Body,"  Quart.  Jour.  Phys.,  vol.  1,  p.  1214  (1908). 

"Lewis,  D.,  Miller,  J.  L.,  and  Matthews,  S.  A.,  "Effects,  on  Blood- 
pressure  of  Various  Anatomical  Components  of  the  Hypophysis,"  Archives  of 
Int.  Med.,  vol.  7,  p.  785  (1911).  See  also  Schickele,  G.,  "  Ueber  die  Herkunft 
der  blutdrucksteigernden  Substanz  in  der  Hypophysis,"  Zcits.  f.  gesam.  Med., 
vol.  1,  p.  545  (1913). 


Am"ju°iyr'i9i4arm*}    Chemistry  of  Pressor  Compounds.  29$ 

Lewis,  Miller  and  Matthews  believe  the  pars  intermedia  to  be 
separated  by  the  hypophyseal  cleft  into  one  portion  closely  con- 
nected with  the  anterior  lobe  and  one  with  the  posterior.  This  may 
explain  why  a  rise  in  pressure  may  follow  the  injection  of  extracts 
of  either  lobe.  They  obtained  a  rise  in  pressure  more  frequently 
from  injections  of  extracts  of  the  anterior  lobe  than  from  those  of 
the  posterior.  Schaefer  and  Herring  were  inclined  to  the  view  that 
the  activity  of  the  anterior  lobe  might  really  be  due  to  postmortem 
infiltration. 

Lewis,  Miller  and  Matthews  found  that  after  removal  of  the 
depressor  compound,  extracts  of  the  pars  intermedia  caused  a  rise 
in  blood-pressure  without  slowing  of  the  pulse-rate.  They,  like 
Howell,  also  noted  that  extracts  of  the  posterior  lobe  caused  a  rise 
in  blood-pressure,  which  was  followed  by  a  fall,  and  that  there  was 
then  a  return  to  the  higher  level.  This  fall  after  the  primary  rise 
was  only  seen  when  extracts  of  the  posterior  lobe  were  used,  and 
they  attributed  this  to  a  second  depressor  principle  which  was  in- 
soluble in  alcohol. 

Osborne  and  Vincent 19  found  that  the  pituitaries  of  various 
teleostean  fishes  exerted  a  pressor  action,  and  claimed  that  the  cen- 
tral part  of  the  infundibular  portion  of  the  ox  pituitary  had  more 
pressor  activity  than  the  peripheral  portion.  In  a  recent  compara- 
tive study  of  the  pituitary  gland  Herring  sums  up  the  work  as 
follows :  "  The  presence  of  active  physiological  principles  in  the 
pituitary  is  associated  with  a  tissue  of  nervous  origin,1'  and  "  there 
is  reason  to  believe  that  the  granules  are  the  histological  represen- 
tatives of  the  active  principles,  and  that  they  are  the  products  of 
part  of  the  epithelial  lobe — the  cells  of  the  pars  intermedia — carried 
to,  elaborated  in,  and  stored  by,  the  pars  nervosa." 

Vincent  and  Sheen  20  took  the  position  that  pressor  principles 
could  be  found  not  only  in  the  pituitaries  and  suprarenals,  but  in 
greater  or  less  extent  in  most  tissues,  and  that  boiling  the  extracts 


19  Osborne,  W.  A.,  and  Vincent,  S.,  "Contribution  to  the  Study  of  the 
Pituitary  Body,"  Brit.  Med.  Jour.  (1900),  vol.  1,  p.  502. 

20  Vincent,  S.,  and  Sheen,  W.,  "Effects  of  Intravascular  Injections  of 
Extracts  of  Animal  Tissues,"  Jour,  of  Physiol.,  vol.  29,  p.  242  (1903).  See 
also  McCord,  C.  P.,  "  Investigation  of  the  Depressor  Action  of  Pituitary 
Extracts,  Archives  of  Int.  Med.,  vol.  8,  p.  609  (1911)  ;  Berlin,  E.,  "  Hemocholin 
und  Neosin,"  Zcits.  f.  Biol.,  vol.  57,  p.  t  (1911). 


t 


296  Chemistry  of  Pressor  Compounds.  {Am'j^yri9Harm' 

made  from  these  organs  usually  enhanced  the  depressor  action  and 
masked  the  pressor  effects.  Miller  and  Miller  found  that,  by  auto- 
clave treatment,  the  pressor  action  of  pituitary  extracts  disappeared, 
while  the  depressor  persisted. 

It  has  been  shown  21  that  in  cats  the  injection  of  extracts  of 
pituitary  glands,  taken  from  almost  any  vertebrate  animal,  will 
increase  the  urinary  secretion.  This  action  has  been  claimed  by 
some  22  to  be  due  to  its  pressor  principle,  but  there  is  physiological 
evidence  to  show  that  the  diuretic  and  pressor  actions  are  due  to 
separate  constituents.  This  diuretic  action  is  confined  to  the  pos- 
terior lobe,  and  second  injections  of  such  extracts  do  not  produce 
tolerance  to  its  diuretic  effect,  but  rather  increase  its  action.  Ex- 
tracts of  pituitary  glands  taken  from  some  animals  have  little  or 
no  effect  on  blood-pressure,  yet  exert  a  diuretic  action.23 

It  has  been  found  that  extracts  of  pituitary  glands  exert  an 
action  on  various  organs  which  are  supplied  with  unstriated  muscles, 
such  as  the  uterus,24  intestines,  bladder,  etc.  Recently  Barger  and 
Dale  have  shown  that  various  amines  will  not  only  produce  a  rise 
in  blood-pressure,  but  also  affect  various  organs  with  unstriated 
muscles.  In  this  case  the  action  is  on  the  extreme  terminals  (re- 
ceptor bodies)  of  the  sympathetic  nerves  supplying  these  organs, 
and  these  observers  have  designated  this  action  as  "  sympathomi- 
metic." In  the  case  of  the  pituitary  extracts  the  action,  at  least  on 
the  uterus,  seems  to  be  different,  and  is  believed  by  Dale  to  be  on 
the  muscles  rather  than  on  the  sympathetic  nerve-endings.  This 
view  is  supported  by  the  experiments  of  Paton  and  Watson  on 
birds. 

The  pressor  principle  and  the  one  which  causes  uterine  contrac- 
tions may  not  necessarily  be  the  same,  or,  at  least,  all  of  the  uterine 

21  Schaefer,  E.  A.,  and  Herring,  P.  T.,  "  Action  of  Pituitary  Extracts 
upon  the  Kidney,"  Philos.  Trans.  Roy.  Soc.  London,  Ser.  B,  vol.  199,  p.  1 
(1908). 

22  Houghton,  E.  M.,  and  Merrill,  C.  H.,  "  Diuretic  Action  of  Adrenalin 
and  the  Active  Principle  of  the  Pituitary  Body,"  Jour.  Amer.  Med.  Assoc., 
vol.  51,  p.  1849  (1908). 

23  Herring,  P.  T.,  "  Further  Observations  upon  the  Comparative  Anatomy 
and  Physiology  of  the  Pituitary  Body,"  Quart.  Jour.  Exper.  Physiol.,  vol.  6, 
P-  73  (1913). 

24  Bayer,  G.,  and  Peter,  L.,  "  Zur  Klenntniss  des  Neurochemismus  der 
Hypophyse,"  Arch.  f.  exper.  Path.,  vol.  64,  p.  204  (1911). 


Am.^jour^Pharm. j     Chemistry  of  Pressor  Compounds.  297 

action  may  not  be  due  to  the  pressor  principle.  Engeland  and 
Kutscher  25  have  attempted  to  isolate  the  compound  which  causes 
contractions  in  the  cat  uterus.  They  attributed  this  action  to  cholin, 
as  they  isolated  this  base  from  pituitaries  and  found  that  control 
solutions  of  cholin  caused  contractions  of  the  isolated  uterus.  Gau- 
trelet  had  previously  found  cholin  in  the  hypophysis.  Engeland 
and  Kutscher  believe  the  pressor  principle  to  be  -different  from  the 
one  which  acts  on  the  uterus. 

Bayer  and  Peter  26  claim  that  the  pituitary  principle  which  stim- 
ulates the  autonomic  nerve-endings  of  the  intestines  resides  in  the 
posterior  lobe  only  and  is  not  specific  for  this  organ,  and  that  the 
portion  of  the  lobe  insoluble  in  alcohol  causes  inhibition,  while  the 
portion  soluble  in  alcohol  causes  increased  activity.  On  isolated 
bronchial  muscle,  extracts  of  the  hypophysis,  histamine,  and  Witte's 
pepton  caused  no  contraction.27 

Like  the  secretion  of  the  ovaries,  extracts  of  the  pituitary  glands 
also  increase  the  secretion  of  the  mammary  gland.28  According  to 
Herring,20  extracts  of  the  pituitary  gland  of  skates  produce  an 
increase  in  mammary  secretion,  but  do  not  produce  a  rise  in  blood- 
pressure  or  increase  in  urinary  secretion. 

The  apparent  similarity  30  in  some  of  the  actions  of  pituitary  ex- 

25  Engeland,  R.,  and  Kutscher,  F.,  "  Ueber  einige  physiologischen  wichtige 
Substanzen,"  Zeits.  f.  Biol.,  vol.  57,  p.  527  (1912)  ;  Schickele,  G.,  "Ueber  die 
Herkunft  der  blutdrucksteigernden  Substanz  in  der  Hypophysis,"  Zeits.  f. 
d.  ges.  exp.  Med.,  vol.  1,  p.  545  (1913)  ;  Bell,  W.  B.,  "Pituitary  Body,"  Brit. 
Med.  lour.  (1900),  vol.  2,  p.  1609. 

26  Bayer,  G.,  and  Peter,  L.,  "  Zur  Kenntniss  des  Neurochemismus  der 
Hypophyse,"  Archiv.  f.  exper.  Path.,  vol.  64,  p.  204  (1911). 

27  Trendelenburg,  P.,  "  Physiologische  und  pharmakologische  Untersuch- 
ungen  an  der  isolierten  bronchial  Muskulatur,"  Archiv.  f.  exper.  Path.,  vol. 
69,  p.  106  (1912). 

28  Ott,  L,  and  Scott,  J.  C.,  Proc.  Soc.  Exper..  Biol,  vol.  1,  p.  1911)  ; 
Schaefer,  E.  A.,  "  On  the  Effect  of  the  Pituitary  and  Corpus  Luteum  Ex- 
tracts on  the  Mammary  Secretion  in  the  Human  Subject,"  Quart.  Jour.  Exper. 
Physiol,  vol.  6,  p.  17  (1913)  ;  Gavin,  W.,  "On  the  Effects  of  Administra- 
tion of  Extracts  of  Pituitary  Body  and  Corpus  Luteum  to  Milch  Cows," 
ibid.,  p.  13. 

20  Herring,  P.  T.,  "  Contribution  to  the  Comparative  Physiology  of  the 
Pituitary  Body,"  Quart.  Jour.  Physiol,  vol.  1,  p.  261  (1908). 

30  Claude,  H.,  and  Baudoin,  A.,  "  Sur  les  effets  de  certains  extraits  hypo- 
physaires,"  Comp.  rend.  Acad,  des  Sci.  Paris,  vol.  153,  p.  1513  (1911)  ;  v. 
Frankl-Hochwart,  L.,  and  Frohlich,  A.,  "  Zur  Kenntniss  der  Wirkung  des 
Hypophysins,"  Archiv.  f.  exper.  Path.,  vol.  63,  p.  347  (1910). 


298  Chemistry  of  Pressor  Compounds.     { Am jlf1y"ri9Harm* 

tracts  with  those  of  epinephrin  suggested  the  identity,  or  at  least  a 
close  chemical  relationship  of  the  pressor  principle  of  the  pituitary 
with  that  of  the  adrenal  glands,  hut  Allers  and  Houssay  31  proved 
that  the  chemical  reactions  of  pituitary  pressor  extracts  were  dif- 
ferent from  those  of  epinephrin,  and  the  method  used  for  isolating 
epinephrin  from  the  suprarenal  glands  failed  to  yield  this  compound 
when  tried  on  pituitary  extracts.  Meyers  32  has  shown  that,  while 
repeated  intravenous  injections  of  epinephrin  produced  arterial 
degeneration  in  rabbits,  pituitrin  caused  almost  no  vascular  changes ; 
and  Cramer 33  has  claimed  that,  while  epinephrin  when  mixed 
with  formaldehyde  rapidly  lost  its  pressor  activity,  Pituitrin  when 
so  treated  retained  this  activity.  Again,  Meltzer  34  claims  there  is  a 
difference  in  action  on  the  enucleated  eye  between  epinephrin  and 
the  commercial  preparation  of  pituitary  glands.  Allers  noted  that 
Pituitrin,  which  is  a  dilute  acetic  extract  of  the  glands,  gave,  like 
epinephrin,  when  treated  with  an  alkali,  an  odor  of  an  alkylamin. 
Fiihner 35  has  recently  stated  that  B-iminazolylethylamine  hydro- 
chloride, or  Histamin,  when  injected  intravenously  into  rabbits,  pro- 
duces the  same  effects  on  blood-pressure  and  the  respiration  as 
Pituitrin,  but  admits  it  is  not  the  active  principle  of  the  pituitary 
gland,  as  this  substance  is  more  toxic  than  a  corresponding  amount 
of  Pituitrin,  and  while  repeated  injections  of  B-iminazolylethyla- 
mine will  give  some  tolerance  to  the  injections  of  the  same,  yet  will 
not  give  immunity  to  Pituitrin,  so  that  at  one  time  Fiihner  suggested 
that  the  active  principle  of  the  pituitary  gland  is  not  B-iminazolyle- 
thylamine, but  related  to  it.    However,  Einis  36  found  that  the.  action 


31  Allers,  R.,  "  Zur  Kenntniss  der  wirksamen  Substanz  in  der  Hypo- 
physis," Munch,  med.  Woch.,  vol.  56,  pt.  2,  p.  1474  (1909)  ;  Houssay,  B.  A. 
"'  Estudios  sobre  la  accion  de  los  cxtractos  hipofisiarios,"  p.  159. 

32  Meyers,  M.  K.,  "  Die  Wirkung  von  intravenosen  Injektionen  von  Hypo- 
physenextrakt,"  Cent.  d.  Allg.  Path.,  vol.  20,  p.  109  (1909)  ;  Etienne  and 
Parrisot,  Arch,  de  med.  Expcr.,  July,  1908,  found  slight  lesions. 

33  Cramer,  W.,  "  On  the  Inactivation  of  Adrenalin  in  vitro  and  in  vivo," 
Proc.  Physiol.  Soc,  p.  xxxvi ;  Jour,  of  Physiol.,  vol.  42  (1911). 

34  Meltzer,  S.  J.,  "  Influence  of  the  Infundibular  Portion  of  the  Hypophy- 
sis upon  the  Pupil,"  Proc.  Soc.  Expcr.  Biol.,  vol.  9,  p.  103  (1912).  See  also 
Kepinow,  p.  261. 

35  Fiihner,  H.,  "  Das  Pituitrin  und  seine  wirksamen  Bestandteile,"  Munch, 
med.  Woch..  vol.  59,  p.  852  (1912)  ;  Kaufmann,  P.,  "Ueber  den  Einfluss  der 
Organextrakte  auf  die  Blutgefasse,"  Zcit.  f.  Physiol,  vol.  27,  p.  532. 

36  Einis,  W.,  "  Ueber  die  Wirkung  des  Pituitrin  und  B-imidazolylethyl- 
amine  auf  die  Herzaktion,"  Biochcm.  Zeits.,  vol.  52,  p.  96. 


Am'juiyr'i^4arm'}    Chemistry  of  Pressor  Compounds.  299 

of  B-iminazolylethylamine  on  the  frog  heart  was  different  from  that 
of  Pituitrin.  It  is  difficult  to  understand  how  this  substance  could 
be  the  active  pressor  constituent  of  the  pituitary  glands,  because  in 
carnivora  it  produces  a  fall  in  blood-pressure,  although  it  produces 
a  rise  in  pressure  in  herbivora,  while  pituitary  extracts  cause  a  rise 
in  rabbits  and  dogs.37 

Kepinow  has  pointed  out  a  synergism  between  the  action  of  epine- 
phrin  and  pituitary  extracts;  that  is,  small  doses  of  epinephrin  are 
claimed  to  increase  the  action  of  pituitary  extracts  so  that  the  com- 
bined action  corresponds  to  more  than  their  simple  addition.  Small 
inactive  doses  of  extracts  of  the  hypophysis  increase  the  action  of 
epinephrin  on  rabbits ;  in  other  words,  the  animal  becomes  sensi- 
tized.38 

Chemical  Experiments. 

Considerable  chemical  work  has  been  done  on  the  pituitary 
glands,  but  apparently  no  pure  pressor  compound  has  as  yet  been 
definitely  isolated.  Calcium,  phosphorus,  bromine,  arsenic,  guanin, 
and  cholin  have  been  found  to  occur  in  the  glands,  and,  while  iodine 
was  suspected,  owing  to  an  apparent  histological  resemblance  be- 
tween the  thyreoid  and  pituitary  glands,  as  yet  it  has  not  been  proved 
to  be  present. 

According  to  our  experiments,  repeated  evaporation  of  extracts 
of  the  pituitary  gland,  and  also  putrefaction,  will  cause  rapid  dimi- 
nution in  pressor  activity.  Schaefer  and  Herring 39  noted  that 
trvptic  digestion  for  18  hours  did  not  destroy  its  diuretic  or  pressor 
action,  and  that  peptic  digestion,  while  it  did  not  injure  its  diuretic 
action,  changed  the  character  of  the  pressor  action. 

Oliver  and  Schaefer  found  that  aqueous  extracts  of  pituitary 
glands  could  be  boiled,  at  least  for  a  short  time,  with  little  or  no  loss 
in  pressor  activity.  Aldrich  40  extracted  the  fresh  infundibular  por- 
tion of  the  gland  with  dilute  acetic  acid  and  then  removed  the  coag- 

37  Dale,  H.  H.,  and  Laidlaw,  P.  P.,  "  Physiological  Action  of  B-iminaz- 
olylethylamine," Jour.  Physiol.,  vol.  41,  p.  318  (1910-11). 

38  Kepinow,  "  Ueber  den  Synergismus  von  Hypophysis  Extrakt  und  Adre- 
nalin," Arch.  f.  expcr.  Path.,  vol.  67,  p.  247  (1912). 

:!n  Schaefer  and  Herring,  /.  c,  p.  22. 

40  Aldrich,  T.  B.,  "  Preliminary  Contribution  to  the  Chemistry  of  the 
Infundibular  Portion  of  the  Pituitary  Body,"  Amer.  Jour.  Phys.  (1907-08), 
vol.  21,  p.  xxiii. 


300  Chemistry  of  Pressor  Compounds.  {Am'/U0iyr'i91i4arm' 

ulable  proteins  by  means  of  heat  and  nitration.  Aqueous  extracts 
of  undried  pituitaries  pass  through  filter  paper  with  the  greatest 
difficulty,  but  after  thorough  coagulation  of  the  proteins  the  extracts 
filter  readily. 

As  Lewis,  Miller  and  Matthews  showed  that  a  pressor  action 
could  be  obtained  from  all  portions  of  the  gland,  we  used  the  whole 
gland  and  avoided  the  tedious  mechanical  labor  of  removing  the 
posterior  portion.  The  fresh  beef  glands  were  ground  in  a  meat- 
chopper and  extracted  twice  with  o.i  per  cent,  acetic  acid,  and,  after 
squeezing  through  cheese-cloth,  the  extract  was  coagulated  on  the 
water-bath  and  the  filtrate  evaporated  in  vacuo.  This  gradually 
colored  during  evaporation  and  left  a  brownish-yellow,  gummy,  non- 
crystalline mass,  which,  on  intravenous  injection  into  dogs,  would 
induce  a  marked  rise  in  blood-pressure. * 

On  treatment  with  hot  methyl  alcohol  (Merck's  highest  purity) 
all  the  color  and  activity  went  into  the  alcohol.  This  solution  gave 
a  heavy  precipitate  on  the  cautious  addition  of  a  drop  or  two  of  con- 
centrated sulphuric  acid,  which  redissolved  with  an  excess  of  the 
acid.  This  precipitate  dissolved  in  water,  forming  a  reddish  solu- 
tion, and  produced  a  marked  rise  in  blood-pressure.  When  freshly 
precipitated  it  dissolved  in  hot  methyl  alcohol  or  ethyl  alcohol  (com- 
mercial 95  per  cent.),  but  if  washed  with  ether  and  placed  in  the 
desiccator  became  insoluble  in  either  alcohol.  At  first  we  believed 
this  to  be  a  true  sulphate  mixed  with  calcium,  but  found  that 
after  further  purification  it  failed  to  be  reprecipitated  from  methyl 
alcohol  by  sulphuric  acid,  hence  we  argued  that  the  first  precipita- 
tion was  merely  mechanical.  This  precipitate,  dissolved  in  water, 
or  the  acetic-acid  extract  of  the  glands,  gave  a  heavy  precipitate 
with  lead  acetate  or  lead  subacetate,  mercuric  chloride  or  uranium 
acetate. 

The  filtrate  after  uranium  acetate  precipitation  was  active,  but 
uranium  gave  no  precipitate  if  the  lead  precipitation  had  been  com- 
pletely done.  Mercuric  chloride  also  gave  a  heavy  precipitate  and 
the  filtrate  was  active.  Gold  chloride,  platinum  chloride,  silver 
acetate,  picric  acid,  picolinic  acid,  and  benzoyl  chloride  with 
sodium  hydrate,  all  gave  precipitates  with  a  solution  of  the  sulphuric- 


*  Note. — These  dogs  were  narcotized  with  ether  and  morphine  and  the 
vagi  nerves  were  usually  cut.  The  most  satisfactory  results  were  obtained 
by  using  young  dogs.    Older  or  large  ones  did  not  seem  to  respond  well. 


Am'jSyr'i9i4arm'}    Chemistry  of  Pressor  Compounds.  301 

acid-alcohol  precipitate,  or  from  the  acetic  acid  extract  of  the  glands, 
but  as  yet  we  have  been  unable  to  obtain  an  active  pressor  compound 
from  any  of  these  precipitates.  Aldrich  claims  to  have  obtained  an 
active  crystalline  picrate  by  precipitation  with  picric  acid  from  a 
concentrated  solution  of  the  glands  purified  by  precipitation  with 
uranium  acetate,  but  he  has  published  no  analyses  of  this  picrate. 

We  found  that  sodium  tungstate  gave  an  active  precipitate  which 
was  soluble  in  acetic  acid,  but  a  control  solution  of  sodium  tung- 
state also  caused  a  rise,  hence  we  cannot  say  whether  or  not  the 
activity  was  due  to  the  reagent.  We  have  been  unable  to  throw  out 
an  active  base  by  means  of  alkalies,  or  any  active  combination  of 
it  by  means  of  aluminum  hydroxide,  but  obtained  an  amine  odor  on 
treatment  of  active  solutions  with  an  alkali.  Magnesium  oxide 
seemed  to  carry  down  mechanically  some  of  the  pressor  compound. 
No  active  volatile  compound  was  obtained  by  alkaline  distillation. 

A  marked  odor  of  skatol  arose  on  treating  Pituitrin  with  hydro- 
gen peroxide,  and  the  solution  lost  its  pressor  action.  Schaefer  and 
Herring  state  that  extracts  of  the  pituitary  glands,  when  treated 
with  this  reagent,  still  induced  an  increased  urinary  secretion,  but 
produced  merely  a  slight  rise  in  blood-pressure.  In  their  experi- 
ments reducing  agents,  such  as  zinc  and  hydrochloric  acid,  were 
without  effect,  either  on  the  diuretic  or  on  the  pressor  action  of  such 
preparations. 

Recently  Baudouin  41  claims  that  he  has  obtained  an  ash- free, 
hygroscopic  compound  by  dissolving  the  dried  acetic  acid  extract  in 
absolute  ethyl  alcohol  and  freezing  out  the  active  substance.  From 
methyl  alcohol  solution  of  the  acetic  acid  extract  we  succeeded  in 
freezing  out,  by  means  of  solid  carbon  dioxide,  an  almost  white 
precipitate  which  caused  a  marked  rise  in  blood-pressure,  and  the 
filtrate  was  only  slightly  active,  but  on  resolution  of  this  active  pre- 
cipitate, freezing  gave  no  precipitate. 

After  precipitating  with  lead  subacetate  and  removing  as  much 
of  the  lead  as  possible  by  phosphoric  or  sulphuric  acid  the  filtrate 
was  still  active,  even  though  hydfogen  sulphide  was  used  to  remove 
the  last?  traces  of  lead ;  but  if  hydrogen  sulphide  alone  was  used  to 
remove  the  lead,  both  the  filtrate  and  precipitate  became  inactive, 
but  solutions  of  the  glands  to  which  lead  had  not  been  added  were 


41  Baudouin,  A.,  "  Sur  le  recherche  du  principe  actif  de  l'hypophyse," 
Comp.  rend.  Soc.  de  Biol,  vol.  74,  p.  1138  (1913). 


302  Chemistry  of  Pressor  Compounds.     { Am'jui°yuri9i4arm' 

uninjured  by  hydrogen  sulphide  alone,  hence  the  active  pressor  com- 
pound must  have  been  carried  down  with  the  lead  sulphide,  but 
as  yet  we  have  been  unable  to  recover  it  from  the  lead  sulphide  pre- 
cipitate. From  this  precipitation  and  from  the  fact  that  it  is  com- 
pletely removed  or  destroyed  by  animal  charcoal  we  argued  a  high 
molecular  weight,  although  this  does  not  necessarily  follow.  After 
thorough  precipitation  with  lead  subacetate  and  freeing  from  lead 
with  phosphoric  acid  the  filtrate  gave  no  biuret  reaction,  but  gave  a 
reaction  with  Folin's  hydroxy-phenyl  reagent.  After  lead-sub- 
acetate  precipitation  and  removal  of  the  lead,  neither  zinc  sulphate 
nor  ammonium  sulphate  (saturated  solution)  gave  a  precipitate. 

In  connection  with  one  of  our  students  we  had  begun  some  work 
with  Caviar  pepton  *  and  found  that  the  intravenous  injection  into 
a  dog  of  a  few  milligrams  of  it  would  produce  a  marked  and  per- 
sistent rise  in  blood-pressure.  This  at  once  suggested  that  there 
was  a  pepton  which  would  cause  a  rise  in  blood-pressure,  or  that  the 
rise  which  followed  the  injection  of  Caviar  pepton  was  due  to  cal- 
cium or  barium,  supposedly  used  in  neutralizing  the  acid  used  in  the 
hydrolysis,  or  to  amino-compounds  arising  in  the  formation  of  the 
pepton,  or  to  albumose,  or  to  some  other  unknown  compound  formed 
along  with  peptons. 

We  had  noticed  that  an  iodine  and  potassium  iodide  solution 
would  produce  a  precipitate  from  certain  pituitary  extracts,  and  that 
this  precipitate,  after  decomposing  with  sulphurous  acid,  was  physio- 
logically active,  while  Fiihner  has  shown  that  various  active  prin- 
ciples were  obtained  from  the  phosphotungstic  acid  precipitate,  and 
Aldrich  has  obtained  an  active  principle  by  means  of  picric  acid. 

Now  certain  so-called  peptons  give  precipitates  with  phospho- 
tungstic acid,  iodine  and  potassium  iodide  solution  and  picric  acid, 
and  produce  an  immunity,  or  rather  a  tolerance,  to  a  second  injec- 
tion and  interfere  with  coagulation  of  the  blood.  Pick  and  Spiro  42 
showed  that  the  depressor  action  on  blood-pressure  and  the  anti- 
coagulant action  of  Witte's  pepton  were  not  due  to  peptons  or  albu- 
moses,  but  to  some  other  compound  associated  with  them;  as  Pick 


*  Note. — Supplied  by  the  courtesy  of  the  Hoffmann-La  Roche  Chemical 
Works  of  Grenzbach,  Germany,  through  their  New  York  branch. 

42  Pick,  E.,  and  Spiro,  K.,  "  Ueber  gerinnunghemmende  Agentien,"  Zeits. 
f.  Physiol.  Chem.,  vol.  31,  p.  235  (1900). 


Am' jSr'i9i4arm' }     Chemistry  of  Pressor  Compounds.  303 

says,  "  Es  gibt  Peptone  ohne  Peptonwirkung  unci  Peptonwirkung 
ohne  Peptone."  A  number  of  so-called  peptons  produce  eosinophilia 
in  varying  degrees.  In  some  cases  of  acromegaly,  a  disease  asso- 
ciated with  pituitary  disturbances,  eosinophilia  has  been  reported.43 
Some  pepton  preparations  induce  symptoms  similar  to  those 
which  occur  during  the  anaphylactic  reaction.  Biedl  *3a  claims  that 
Urechia's  results  with  the  intraperitoneal  injections  of  pituitary 
extracts  must  be  interpreted  as  an  anaphylactic  reaction,  and  Pan- 
kow  44  found  that,  after  the  intravenous  injection  of  1—5  c.c.  of 
Pituitrin,  rabbits  became  more  sensitive  to  a  second  injection  made 
in  from  1  to  5  days  after  the  first.  According  to  Fiihner,  the  respi- 
ratory stoppage  from  Pituitrin  resembles  that  from  anaphylaxis.45 
Extracts  of  the  posterior  lobe  are  said  to  accelerate  coagulation  of 
the  blood,  while  those  from  the  anterior  lobe  retard  it.46  Witte's 
pepton,  especially  the  portion  soluble  in  absolute  alcohol,  retards 
coagulation.47 

The  pituitary  gland  contains  various  enzymes,  which  might  form 
pepton-like  bodies.48 

Paal,49  by  treating  albumen  with  hydrochloric  acid,  has  obtained 
products  which  he  calls  salts  of  pepton.  These,  unlike  pepton,  are 
soluble  in  alcohol.  Schrotter  50  claims  to  have  obtained  similar  com- 
pounds with  albumoses.  Peptons  consist  mainly  of  mono-amino 
acids,  and,  according  to  De  Waele,  the  pepton  action  is  primarily 


43Falta,  W.,  "Die  Erkrankungen  der  Blutdrusen,"  1913,  p.  212. 

43a  Biedl,  "  Innere  Sekretion,"  vol.  2,  p.  133  (1913)  ;  Urechia,  C.  J.,  "  Action 
de  l'extrait  hypophysaire  en  injections  intraperitoneales,"  Comp.  rend.  Soc. 
de  Biol,  vol.  65,  p.  278  (1908). 

44  Biedl,  /.  c.,  vol.  2,  p.  136. 

45  Fiihner,  /.  c.,  p.  406. 

40  £mile-Weil,  P.,  and  Boye,  G.,  "  Action  differentes  des  lobes  hypophy- 
saires  sur  la  coagulation  du  sang,"  Comp.  rend.  Soc.  de  Biol.,  vol.  67,  p. 
428  (1909). 

47  Zunz,  E.,  "Apropos  de  Taction  anticoagulante  des  injections  intra- 
veineuses  de  peptone  de  Witte,"  Comp.  rend.  Soc.  de  Biol,  vol.  73,  p.  50 
(1912). 

48  Buetow,  "  Zur  Kenntniss  der  Hypophysenzyme,"  Biochem.  Zeits.,  vol.  54, 
p.  40  (1913). 

49  Paal,  C,  "  Ueber  die  Peptonzalze  des  Eieralbumine,"  Ber.  d.  dcutsch. 
chem.  Gesells.,  vol.  27,  p.  1845. 

60  Schrotter,  Monats.  f.  Chemis.,  vol.  14,  p.  612  (1893). 


304  Chemistry  of  Pressor  Compounds.  {Am'ju?vr'i^i4arm' 

an  amino  action.  From  Witte's  pepton  Pick  51  claims  to  have  sepa- 
rated two  peptons  and  four  albumoses.  However,  as  Haslam  points 
out,  the  methods  do  not  give  sharp  separations.52  Pick  precipitated 
the  primary  albumoses  by  means  of  ammonium  sulphate,  and  sepa- 
rated them  by  alcohol ;  the  hetero-albumoses  53  being  precipitated  by 
weak  ethyl  alcohol,  while  the  proto-albumoses  remained  in  solution 
with  rather  strong  alcohol.  The  hetero-albumoses  would  precipi- 
tate on  dialysis,  and  long  heating  converted  them  into  an  insoluble 
compound  (dysalbumid) .  Witte's  pepton  contained  very  little 
of  the  proto-albumoses.  After  ammonium  sulphate  precipitation 
the  filtrate  yielded  a  product  which  was  called  albumose  C.  On 
treating  the  hetero-albumoses  54  with  hydrochloric  acid  no  tyrosin 
was  obtained,  but  large  amounts  of  leucin  were  found,  while  oxida- 
tion with  potassium  permanganate  yielded  a  compound  believed  to 
be  phenyl-amino-propionic  acid.  The  proto-albumoses  yielded 
tyrosin  and  gave  a  marked  skatol  odor  on  decomposition.  Pick's 
hetero-albumose  contained  no  indol  nucleus,  but  yielded  large 
amounts  of  di-amino  compounds. 

In  one  experiment  Pick  noted  that  both  the  proto-albumoses  and 
hetero-albumoses  obtained  from  Witte's  pepton  caused  a  rise  in 
blood-pressure,  but  as  these  albumoses  had  been  prepared  by  the 
ammonium  sulphate  method  the  rise  may  have  been  due  to  some  of 
the  precipitant,  However,  another  dog  merely  responded  by  a  fall 
in  blood-pressure  when  hetero-albumose  was  injected,  and  in  Popiel- 
ski's  experiments  proto-albumose,  prepared  by  Pick's  method,  pro- 
duced a  rise  in  blood-pressure  in  one  case,  but  a  fall  in  the  second,55 


r'1  Pick,  E.  P.,  "  Zur  Kenntniss  der  peptischen  Spaltungsprodukte  des  Fi- 
brins," Zcits.  f.  physiol.  Chem.,  vol.  28,  p.  219  (1899)  ;  Bcitrag  s.  Chem. 
Physiol.,  vol.  2,  p.  481  (1902).  See  also  Zunz,  E.,  "Die  fractionirte  Abscheid- 
ung  der  peptischen  Verdauungsprodukte  mittelst  Zinksulfat,"  Zeits.  f. 
physiol.  Chem,,  vol.  27,  p.  219  (1899). 

52  Haslam,  H.  C,  "  Separation  of  Proteins,"  Jour.  Physiol.,  vol.  36,  p.  154 
(1907-08). 

53  Kiihne  and  Chittenden. 

54  Schulze,  E.,  "  Untersuchungen  ueber  die  Amidosauren  welche  bei  der 
Zersetzung  der  Eiweissstoffe  durch  Salsaure  und  durch  Barytwasser  ent- 
stehen,"  Zcits.  f.  physiol.  Chem.,  vol.  9,  p.  72. 

55  Popielski,  L.,  "  Ueber  die  Wirkungsweise  des  Chlorbaryium,  Adrenalin 
und  Pepton  Witte  auf  den  peripherischen  vasomotorischen  Apparat,"  Archiv. 
f.  cxper.  Path.,  Stipplementband  1908,  p.  44  1. 


Am'tjfiiy r \$Arm' }     Chemistry  of  Pressor  Compounds.  305 

so  that  Popielski  suspected  barium  to  be  present  in  one  of  the  prepa- 
rations. 

Zunz 50  has  also  found  that  so-called  hetero-albumose,  thio- 
albumose,  deutero-albumose,  and,  especially,  proto-albumose  pro- 
duced a  rise  in  blood-pressure  in  dogs  and  rabbits.  This  rise  was 
followed  by  a  marked  fall,  but,  in  the  case  of  the  proto-albumoses, 
large  amounts  were  necessary  to  produce  the  fall.  Witte's  pepton 
has  been  shown  to  exert  both  a  vaso-constrictor  and  a  vaso-dilator 
action.57  Those  products  of  digestion  which  gave  no  biuret  test 
caused  a  marked  fall  in  blood-pressure.  These  differences  in  re- 
sults may  really  be  due  to  a  difference  in  the  kind  of  proto-albumose 
or  hetero-albumose  used,  as  we  have  no  positive  proof  that  all  fibrin 
from  which  Witte's  pepton  is  obtained  has  necessarily  the  same 
chemical  composition.  Proto-albumose  and  syn-albumose  caused 
recovery  of  the  exhausted  isolated  heart,  while  peptons  caused  sys- 
tolic stoppage. 

Loeper  and  Esmonet 58  have  found  that  a  weak  solution  of  what 
is, called  pepsin  caused  a  slight  fall  in  blood-pressure,  followed  by  a 
rise.  This  rise  was  especially  marked  if  the  pepsin  was  treated 
with  hydrochloric  acid,  and  Popielski 59  noted  that  a  hydrochloric 
acid  preparation  of  the  thymus  gland  would  produce  a  rise  in  blood- 
pressure  with  a  slowed  heart,  and,  like  pituitary  preparations,  pro- 
duced this  rise  even  after  section  of  the  spinal  cord.  This  substance 
was  not  precipitated  by  phosphotungstic  acid,  lead  acetate,  or  by 
platinum  chloride  in  alcoholic  solution,  but  was  precipitated  from 
absolute  alcohol  by  an  absolute  alcoholic  solution  of  mercuric  chlo- 
ride. 

From  this  data  we  argued  that  some  of  the  pressor  activity  was 
due  to  a  compound  with  high  molecular  weight ;  that  is,  one  closely 
allied  to  the  proteins  and  which  would  not  dialyse.  Schaefer  and 
Herring  claimed  that  the  pressor  compound  of  the  pituitary  would 

56  Zunz,  E.,  "  Untersuchungen  ueber  die  Wirkung  von  Albumosen  auf 
Blutdruck  und  Atmung,"  Archives  internat.  de  Physiol.,  vol.  n,  p.  73 ;  "  Ueber 
die  Wirkung  von  Albumosen  auf  das  isolierte  ueberlebende  Schildkroten 
Herz,"  Ibid.,  vol.  10,  p.  290. 

57  Kaufmann,  P.,  "  Ueber  die  Wirkung  des  Witte-Peptones  auf  die  Blut- 
gefasse,"  Zent.  f.  Physiol.,  vol.  27,  p.  724  (1913). 

B8  Loeper  and  Esmonet,  "  Action  vaso-tonique  comparee  des  different  pro- 
duite  de  secretion  gastrique,"  Comp.  rend.  Soc.  de  Biol.,  vol.  70,  p.  8  (1911). 

69  Popielski,  L.,  "  Ueber  eine  neue  blutdrucksteigernde  Substanz  des 
Organismus,"  Zent.  f.  Physiol.,  vol.  23,  p.  137  (1909). 


306  Chemistry  of  Pressor  Compounds.     { Am'ji?y  riSiarm' 

dialyse,  hence  was  not  a  protein.  Using  toluol  as  a  preservative, 
we  lound  tnat  much  of  the  color  dialysed  through  heavy  parchment 
paper,*  and  that  this  colored  solution  was  usually,  though  not  always, 
active,  while  the  liquid  in  the  dialyser  was  intensely  active.  In  this 
connection  it  may  be  remembered  that  Handovsky  and  Pick  showed 
that  there  is  in  the  serum  a  vaso-constrictor  substance  which  is  not 
dialysable  00  and  which  is  not  a  globulin. 

When  our  dialysate  was  collected  in  fractions,  the  last  fractions 
were  without  activity,  whereas  the  fluid  within  the  dialyser  was  still 
very  active,  hence  one  of  the  pressor  principles,  perhaps  the  mother 
substance  of  the  dialysable  pressor  principles,  is  non-dialysable. 
The  depressor  principle  passes  quickly  into  the  dialysate. 

After  long  dialysis  the  residue  in  the  dialyser  gives  a  slight  pre- 
cipitate with  lead  subacetate,  none  with  mercuric  acetate  or  a  solu- 
tion of  iodine  in  potassium  iodide,  but  gives  a  precipitate  with  phos- 
photungstic  acid  or  phospho-molybdic  acid  and  with  stannous  chlo- 
ride or  mercuric  chloride.    It  also  gives  a  strong  biuret  reaction. 

Fuhner  claims  to  have  separated  from  pituitary  extracts  by 
means  of  phosphotungstic  acid  precipitation  and  subsequent  decom- 
position of  the  precipitate  by  means  of  barium  hydrate  various 
pressor  compounds.  On  the  other  hand,  Popielski  claims  that  the 
pressor  activity  is  in  the  phosphotungstic  acid  filtrate.61  Now  it  has 
been  found  that  phosphotungstic  acid  changes  the  chemical  compo- 
sition of  various  compounds,62  hence  there  is  a  possibility  that  phos- 
photungstic acid  would  split  our  non-dialysable  compound  into 
various  amines. 

The  active  non-dialysable  portion  seems  to  correspond  in  some 
respects  to  the  fraction  separated  by  Raper  under  the  name  Ba.63 

*  Note. — Animal  membranes  cannot  be  used  for  dialysis,  as  we  have 
found  that  the  pressor  principles  are  completely  removed  from  the  solution 
by  them  and  cannot  be  recovered. 

60  Handovsky,  H.,  and  Pick,  E.  P.,  "  Ueber  die  Entstehung  vasokon- 
striktorischen  Substanzen  durch  Veranderung  der  Serumkolloide,"  Archiv. 
f.  exper.  Path.,  vol.  71,  p.  62  (1913). 

61  Fuhner,  "  Ueber  die  isolierten  wirksamen  Substanzen  der  Hypophy- 
sen,"  Deutsch.  med.  Woch.,  vol.  39,  p.  491  (1913)  ;  Popielski,  L.,  "Hypo- 
physis und  ihre  Praparate,"  Berl.  klin.  Woch.,  vol.  50,  p.  1156  (1913). 

62 Van  Laer,  H.,  "Nature  of  Amylase,"  Bull.  Acad.  Roy.  Belg.,  vol.  4, 
p.  13;  quoted  in  Chem.  Abstr.,  vol.  8,  p.  510  (1914). 

63  Raper,  H.  S.,  "  Zur  Kenntniss  der  Eiweiss-peptone,"  Beitr.  z.  chem. 
Physiol,  vol.  9,  p.  168  (1907).  See  also  Stookey,  L.  B.,  "Zur  Kenntniss  der 
Eiweisspeptone,"  Beitr.  z.  chem.  Physiol,  vol.  7,  p.  590  (1906). 


Am Jul" r'i9i4arm' }     Determination  of  Phenolphthalein.  307 


A  NEW  METHOD  FOR  THE  DETERMINATION  OF 
PHENOLPHTHALEIN. 

By  Dr.  A.  Mtrkin,  Cincinnati,  O. 

Since  phenolphthalein  has  come  into  extensive  use  as  an  in- 
gredient of  laxative  medicines,  frequent  occasions  arise  for  its  rapid 
and  accurate  determination.  A  few  methods  have  been  proposed, 
but,  with  the  exception  of  one  (Pharm.  Zentrb.,  191 1,  p.  1126),  they 
are  all  gravimetrical,  therefore  troublesome  and  unreliable,  because 
applied  to  an  organic  substance. 

In  trying  to  find  a  volumetric  method  for  its  determination  I 
took  advantage  of  its  property  to  form  a  well-defined  oxime  with 
hydroxylamine.  This  is  the  principle  of  Walker's  method  for 
carvone  determination,  and  of  Nelson  and  his  estimation  of  a  number 
of  ketones,  including  camphor. 

I  first  followed  closely  the  directions  worked  out  by  the  above- 
mentioned  authors,  but  without  result.  I  then  worked  according 
to  Friedlander,  who  first  discovered  the  phenolphthalein  oxime,  but 
the  results  were  still  far  from  satisfactory.  Finally  the  following 
method  was  discovered,  the  results  of  which  are  very  accurate: 

1.  Gramme  phenolphthalein,  0.8  gramme  hydroxylamine  hydro- 
chloride, and  0.52  gramme  90  per  cent,  sodium  hydroxide  solution, 
finely  powdered,  are  dissolved  in  35  to  40  c.c.  of  absolute  alcohol 
and  boiled  for  two  to  three  hours  under  a  reflex  condenser  until  the 
liquid  turns  yellow.  The  liquid  is  then  diluted  with  water,  trans- 
ferred to  a  250  c.c.  volumetric  flask,  10  c.c.  of  10  per  cent.  H2S04 
are  added  and  the  flask  filled  to  the  mark  with  water.  50  C.c.  are 
taken  for  titration.  First  the  acid  is  neutralized,  using  Methyl 
orange  as  indicator.  Then  the  excess  of  hydroxylamine  is  titrated 
with  N/10KOH,  using  phenolphthalein  as  indicator.  A  blank  is 
run,  using  the  same  amounts  of  hydroxylamine,  NaOH  and  alcohol, 
and  boiled  for  the  same  length  of  time.  The  difference  in  the 
number  of  cubic  centimetres  of  N/10  alkali  used  in  the  titration  of 
the  blank  experiment  and  in  the  sample,  multiplied  by  316,  gives  the 
quantity  of  phenolphthalein. 

When  applying  the  method  to  medicinal  tablets,  the  tablets  were 
placed  in  a  cylinder  and  crushed  under  alcohol  with  a  glass  rod. 
The  alcohol  was  decanted  off  through  a  filter  into  a  volumetric  flask 


308  Estimation  of  Morphine  in  Pills,  Etc.  {Am- jJ^yr'Jurm- 

and  the  extraction  and  decantation  continued  until  complete  ex- 
traction was  obtained.  An  aliquot  part  of  the  extract  was  then 
taken  for  the  determination. 

The  method  gives  very  accurate  results  in  the  hands  of  a  careful 
worker.  The  yellow  color  of  the  oxime  does  not  interfere  with  the 
titration,  as  by  proper  dilution  it  colors  the  liquid  only  slightly. 

Tablets  of  phenolphthalein  frequently  contain  milk  sugar  or 
cane  sugar,  but  as  cane  sugar  does  not  give  an  oxime  with  hydrox- 
ylamine,  and  as  milk  sugar  is  practically  insoluble  in  absolute 
alcohol,  they  do  not  interfere  with  the  reaction.  In  case,  however, 
that  the  method  should  give  too  high  a  result,  it  is  better  to  make  a 
volumetric  determination  of  sugar  in  order  to  be  more  sure. 


THE  ESTIMATION  OF  MORPHINE  IN  PILLS, 
TABLETS,  ETC.* 

By  J.  B.  Williams. 

In  a  paper  read  before  the  last  meeting  of  the  Pharmaceutical 
section  of  the  American  Chemical  Society  Mr.  A.  D.  Thorburn  sug- 
gests the  estimation  of  morphine  in  pills,  tablets,  etc.,  by  making 
the  aqueous  solution  alkaline  and  extracting  with  a  mixture  of 
phenyl-ethyl  alcohol  and  benzene,  partially  evaporating  the  alka- 
loidal  solution,  extracting  the  residue  with  n/io  acid  and  titrating 
back  with  n/io  or  N/50  alkali,  using  hematoxylin  as  indicator. 
This  method  has  recently  been  tried  out  with  the  following  results. 
Duplicate  assays  of  a  2  per  cent,  solution  of  morphine  sulphate, 
using  10  c.c.  (  =  0.2  Gm.  morphine  sulphate  or  0.1506  Gm.  anhy- 
drous morphine  alkaloid). 

^=0.1827  Gm.  morphine  sulphate  =  91.35  per  cent. 
5  =  0.1919  Gm.  morphine  sulphate  —  95.95  per  cent. 

The  phenyl-ethyl  alcohol  mixture  did  not  separate  sharply  even 
after  standing  two  hours.  The  morphine  is  apparently  not  dissolved 
in  the  mixture,  but  appears  to  be  held  in  suspension  by  it.  N/50 
alkali  was  used  in  titration,  but  the  end  point  with  hematoxylin  as 
indicator  is  not  sharp  or  satisfactory. 


*  Presented  at  the  meeting  of  die  American  Chemical  Society  at  Wash- 
ington, D.  C,  December,  191 1. 


Am'jui7ri9Pi4arm' }  Estimation  of  Morphine  in  Pills,  Etc.  309 

Two  further  assays  of  the  same  solution  were  made,  but  after 
adding  the  phenyl-ethyl  alcohol  and  benzene  mixture  and  shaking, 
the  separators  were  allowed  to  stand  over  night. 

The  morphine  was  precipitated  through  the  liquid  and  on  the 
sides  of  the  separators.  The  crystals  of  morphine  were  washed  of! 
with  alcohol  and  the  assay  completed.  A,  using  cochineal  as  in- 
dicator, gave  0.1872  Gm.  morphine  sulphate  =  93.6  per  cent.  B, 
with  hematoxylin  as  indicator,  gave  0.1805  Gm.  morphine  sul- 
phate =  90.25  per  cent.  2  c.c.  n/io  acid  and  4  or  5  drops  of  cochi- 
neal were  added  to  B  and  again  titrated,  giving  0.1841  Gm.  morphine 
sulphate  =  92.05  per  cent. 

It  was  thought  that  perhaps  by  replacing  the  benzene  in.  the 
phenyl-ethyl  alcohol  and  benzene  mixture  with  benzene  or  petro- 
leum ether  a  sharper  separation  would  be  obtained.  This  was  tried 
on  a  solution  of  1  Gm.  of  morphine  alkaloid  and  50  c.c.  n/io  acid 
in  100  c.c.  Ten  cubic  centimetres  of  this  solution  titrated  direct 
showed  the  presence  of  0.0981  Gm.  morphine  alkaloid.  Ten  cubic 
centimetres  extracted  by  the  above  modified  method,  replacing  the 
benzene  with  petroleum  ether,  gave  a  sharp  separation  but  low  re- 
sults, 0.08729  Gm.  =  87.29  per  cent,  being  obtained. 

Judging  from  the  limited  number  of  assays  made,  the  method 
is  unsatisfactory  both  as  to  accuracy,  time  required,  and  cost  and 
availability  of  material. 

As  above  stated,  the  morphine  does  not  seem  to  be  dissolved  in 
the  phenyl-ethyl  alcohol  and  benzene  mixture — at  least  not  in  the 
quantity  of  solvent  specified. 

The  U.  S.  P.  gives  the  solubility  of  morphine  in  alcohol  as  1-168 
and  in  chloroform  as  1-1800,  but  in  a  mixture  of  these  two  solvents 
it  will  dissolve  far  more  freely  than  in  either  of  them  separately. 

In  order  to  ascertain  the  relative  solubility  of  the  freshly-pre- 
cipitated alkaloid  in  these  solvents,  morphine  sulphate  was  added 
in  excess  to  alcohol,  chloroform,  and  a  mixture  of  alcohol  1  part 
and  chloroform  2  parts,  respectively.  Sufficient  ammonia  was  added 
to  liberate  the  alkaloid,  and  the  flasks  shaken  for  two  or  three 
hours.  Ten  cubic  centimetres  of  the  filtered  liquid  were  then  evap- 
orated to  dryness  and  the  alkaloid  estimated  volumetrically  as  crys- 
talline morphine.  The  averages  of  several  estimations,  weight  to 
volume,  were  as  follows : 


310  Estimation  of  Morphine  in  Pills,  Etc.  { Am'Jl'J10;Jiri9uarm- 

Solvent.  Wt.  of  cryst.  morphine  in  10  c.c.      Solubility  w-v. 

Alcohol   0.0547  Gm  1-182.6 

Chloroform   0.0110  Gm  1-909 

Alcohol        1  )  r  .  >  n  s 

~U1      r  \  0-1316  Gm  1-76 

Chloroform  2  J 

The  solubility  of  precipitated  morphine  crystals  (dried  below 
6o°  C.)  in  the  same  solvents  was  also  determined,  the  average  of  a 
number  of  estimations  being : 

Solvent.  Wt.  of  cryst.  morphine  in  10  c.c.      Solubility  w-v. 

Alcohol   0.0421  Gm  1-237.5 

Chloroform   0.0025  Gm   1-4000 

Alcohol         1  1  .0  r  o 

~,  ,      ,   0.1258  Gm  1-80 

Chloroform  2  J 

Also  the  solubility  of  crystalline  morphine  in  mixtures  containing 
varying  proportions  of  alcohol  and  chloroform: 

Solvent.  Wt.  of  cryst.  morphine  in  10  c.c.  Solubility. 

Alcohol        1  I  Q  I       Qm  ^  ^ 

Chloroform  I  J 


Alcohol  1 
Chloroform  2 


\  0.1258  Gm  1-80 


Alcohol        1  1   o  o879  Gm  1-114 

Chloroform  4  J 


Alcohol  1 
Chloroform  8 


.0.512  Gm  I-I95.5 


Based  on  these  experiments,  the  following  assay  method  is 
recommended : 

A  number  of  pills  or  tablets,  or  a  quantity  of  the  sample  for 
assay  containing  not  more  than  0.5  Gm.  morphine  (preferably  from 
0.1  to  0.2  Gm.),  is  dissolved  in  a  few  cubic  centimetres  of  acidulated 
water,  either  in  a  separator  or  in  a  beaker,  and  then  transferred  to 
a  separator,  keeping  the  volume  of  the  liquid  as  small  as  possible 
(from  5  to  10  c.c.)  ;  add  from  15  to  25  c.c.  of  mixture  of  alcohol  1 
part  and  chloroform  2  parts  by  volume  and  2  or  3  c.c.  of  10  per  cent, 
solution  of  ammonia,  or  sufficient  to  make  distinctly  alkaline. 
Stopper  the  separator  and  shake  well  for  2  or  3  minutes.  After 
separation,  which  usually  takes  place  inside  of  a  few  minutes,  draw 
off  the  chloroformic  solution,  filter  through  cotton,  well  wet  with 
chloroform,  into  a  wide-mouth  flask  or  beaker  of  about  150  c.c. 
capacity.    Repeat  the  extraction  with  two  further  like  portions  of 


Amjufy?i'9iP4harm'}  Estimation  of  Morphine  in  Pills,  Etc.  311 

the  alcohol  chloroform  mixture  and  then  with  three  10  c.c.  portions 
of  chloroform. 

Evaporate  the  alcohol  chloroform  solution  on  a  water-bath  under 
a  current  of  warm  air  to  dryness,  add  a  few  cubic  centimetres  of 
alcohol  and  again  evaporate.  Dissolve  the  residue  in  an  excess  of 
n/io  acid  and  titrate  back  with  N/50  alkali,  using  cochineal  as  in- 
dicator. Each  cubic  centimetre  of  acid  neutralized  by  the  alkaloid  = 
0.0301  Gm.  of  crystalline  morphine  or  0.0376  Gm.  morphine  sulphate. 

Following  are  some  of  the  results  obtained  by  this  method.  A 
2  per  cent,  solution  of  morphine  alkaloid  was  prepared  and  assayed. 

(  0.0976  Gm.  =  97.6    per  cent. 

"5  c.c.  =  0.1  Gm.  morphine  gave  {         ,  ^    ,  ^ 

°  .    fi  {  0.0976  Gm.  —  97.6    per  cent. 

  ,•  f  0.1940  Gm.  —  97.0    per  cent. 

10  c.c.  —  0.2  Gm.  morphine  gave  J      ^  * 

{  0.1952  Gm.  =  97.59  per  cent. 

20  c.c.  =  0.4  Gm.  morphine  gave  {  °-390i  Gm.  =  97.52  per  cent. 

10.3901  Gm.  =  97.52  per  cent. 

A  2  per  cent,  solution  of  commercial  morphine  sulphate. 

j  0.09944  Gm.  =  99.44  per  cent. 

5  c.c.  =  0.1  Gm.  morphine  sulphate  gave....!  ^   

J  .  "  (  0.09944  Gm.  —  99.44  per  cent. 

^  u-         1  u  j.  f  0.1981    Gm.  =  99.06  per  cent. 

10  c.c  =  0.2  Gm.  morphine  sulphate  gave....  \      y  ^  F 

{  0.1981    Gm.  =  99.06  per  cent. 

20  c.c.  =  0.4  Gm.  morphine  sulphate  gave...  j  °-3932    Gm.  =  98.3"  per  cent. 

I  0.3940    Gm.  =  98.5    per  cent. 

The  quantity  of  solvent  used  in  the  extraction  of  this  sample  was 
the  same  in  each  case. 

Two  weighed  quantities  of  another  sample  of  morphine  sulphate 
0.0535  and  0.0560  Gm.  gave  0.05395  and  0.05634  Gm.  respectively 
when  extracted. 

A  quantity  of  morphine  alkaloid  (1  Gm.)  was  dissolved  in  ex- 
actly 50  c.c.  n/io  acid,  then  made  up  to  100  c.c.  with  distilled  water ; 
of  this  solution  two  10  c.c.  portions  were  titrated  and  required  for 
neutralization  8.7  c.c.  and  8.7  c.c.  of  N/50  alkali,  showing  the  pres- 
ence of  0.09813  Gm.  of  morphine  in  each.  Two  other  10  c.c.  por- 
tions extracted  by  the  above  method,  the  residue  dissolved  in  5  c.c. 
n/io  acid  and  titrated,  required  8.7  c.c.  and  8.8  c.c.  of  N/50  alkali 
to  neutralize,  corresponding  to  0.09813  Gm.  and  0.09752  Gm.  re- 
spectively. 


312 


Estimation  of  Morphine  in  Pills,  Etc.  {Am- ^ 


Several  other  samples  of  morphine  sulphate  and  morphine  alka- 
loid gave  equally  good  results.  A  large  number  of  pills  and  tablets 
assayed  by  this  method  gave  results  approximating  closely  the  theo- 
retical content. 

The  advantages  of  this  method  are  accuracy,  simplicity,  and 
shortness  of  time  required  for  completion,  duplicate  assays  being 
easily  completed  inside  of  two  hours,  except  when,  owing  to  the 
presence  of  sugar  or  gummy  matter  in  the  sample,  slight  emulsions 
may  form,  requiring  a  little  more  time  for  separation,  although  this 
can  usually  be  prevented  by  keeping  the  aqueous  portion  to  as  small 
a  volume  as  possible. 

Since  December,  1909,  nearly  one  hundred  assays  by  this  method 
have  been  made  by  the  writer  and  so  far  practically  no  trouble  has 
been  experienced.  Of  course,  this  method  is  available  only  where 
the  morphine  is  not  combined  with  other  alkaloids,  the  identity  of 
the  alkaloid  being  taken  for  granted,  but  as  a  check  on  the  manu- 
facture of  pills,  tablets,  etc.,  it  has  given  good  results. 

,  A  comparison  of  results  obtained  by  the  two  methods  follows. 


10  C.C.  OF  A  2  PER  CENT.  SOLUTION   MORPHINE  SULPHATE. 

By  Alcohol-chloroform  Method. 

I  0.1984  Gm.  morphine  sulphate  =  99.2  per  cent. 

77   0.1976  Gm.  morphine  sulphate  =  98.8  per  cent. 

By  Phenyl-Ethyl  Alcohol  and  Benzene  Method. 

A   =0.1827  Gm.  =  91.35  per  cent. 

B   =0.1919  Gm.  =  95.95  per  cent. 

The  solution  containing  1  Gm.  morphine  alkaloid  and  50  c.c. 
n/io  acid  in  100  c.c.  gave  by  direct  titration  0.0981  Gm.  morphine 
alkaloid  in  10  c.c.  and  by  extraction. 

By  alcohol-chloroform.  By  phenyl -ethyl-alcohol  &  B.  mod. 

1  0.09812  Gm.  =98.12  per  cent   \ 

tt  n  >.  *  4.  1  =0.08729  Gm.  =  87.29  per  cent. 
II  0.09752  Gm.  =  97.52  per  cent          J  /  y  '   *  v 

Time  required  for  phenyl-ethyl  alcohol  method,  4  to  7  hours. 
Time  required  for  alcohol-chloroform  method,  2  to  3  hours. 


Analytical  Department,  Parke,  Davis  &  Co.,  Detroit,  Mich. 


Am.  Jour.  Pharm. 
July,  1914. 


Bichloride  of  Mercury  Tablets. 


313 


BICHLORIDE  OF  MERCURY  TABLETS  AND  BICHLORIDE 


In  presenting  a  paper  on  such  a  hackneyed  subject  as  "  Bichloride 
of  Mercury  Tablets  and  Bichloride  Tablet  Legislation,"  I  am  well 
aware  that  I  may  be  trying  your  patience  on  a  subject  that  you  may 
perhaps  consider  as  threadbare.  My  association  with  and  study 
of  this  subject,  however,  convince  me  that  this  is  not  a  dead  subject, 
but  contains  several  problems  directly  associated  with  the  duties  of 
the  druggist  and  which  pharmacists  themselves,  in  a  very  large 
measure,  must  decide. 

The  extensive  use  of  corrosive  sublimate  in  this  form  has  justi- 
fied the  decision  of  the  Committee  of  Revision  of  the  U.  S.  P.  to 
introduce  an  official  formula  and  by  this  means  to  endeavor  to 
formulate  additional  safeguards  to  life  in  their  use.  The  articles 
that  have  appeared  in  the  medical,  pharmaceutical  and  lay  press, 
as  well  as  the  discussion  in  the  committee,  demonstrate  that  this  is 
a  live  subject,  and  associated  with  it  are  several  questions  still  to  be 
settled. 

In  the  official  recognition  of  the  tablet  of  mercuric  chloride  the 
U.  S.  P.  is  only  following  the  example  of  most  of  the  pharmacopoeias 
that  have  been  revised  in  recent  years.  A  study  of  the  foreign 
formulas  and  a  comparison  of  these  and  likewise  of  the  commonly 
used  American  formulas  are  interesting. 

In  American  practice,  either  the  Wilson  formula  containing-  a 
mixture  of  mercuric  chloride  and  ammonium  chloride  or  the  Bernay 
formula  containing  mercuric  chloride  and  citric  acid  has  hem 
almost  exclusively  used.  In  Europe  the  formula  proposed  by 
Angerer  for  Pastilla  Hydrargyri  bichlorati  has  been  the  type  fol- 
lowed.   His  formula  was : 


TABLET  LEGISLATION.1 


By  George  M.  Beringer. 


Mercury  bichloride, 
Sodium  chloride,  aa 
Eosin   


1.0  Gm. 


0.5  Kg. 


1  Read  before  the  New  Jersey  Pharmaceutical  Association,  Lake 
Hopatcong,  N.  J.,  June  17,  1914. 


3H 


Bichloride  of  Mercury  Tablets. 


{Am.  Jour.  Pharm. 
July,  1914. 


Mix  the  salts  and  color  the  mixture  with  the  eosin  dissolved  in 
water.  Allow  the  mixture  to  dry  in  the  air  and  compress  into 
portions  weighing  i  or  2  grammes  each. 

The  German  Pharmacopoeia  iv  (1900),  and  again  in  the  fifth 
edition  (1910),  adopts  the  title  "  Pastilli  Hydrargyri  bichlorati  "  and 
directs  that  from  a  mixture  of  equal  parts  of  mercuric  chloride  and 
sodium  chloride  colored  with  a  red  coal-tar  dye  are  to  be  made 
cylinders  twice  as  long  as  thick  and  weighing  1  or  2  grammes  each. 
Sublimate  pastilles  must  be  dispensed  in  sealed  bottles  labelled 
"  Poison, "  and  each  pastille  must  be  wrapped  in  black  paper  on 
which  is  printed  in  white  the  word  "  Poison  "  and  the  content  of 
mercuric  chloride  stated  in  grammes. 

The  Swedish  Pharmacopoeia  (1901),  under  the  title  of  Pastilli 
chlorati  hydrargyria,  directed  that  "  Sublimate  pastilles  "  should  be 
hard  cylinders  or  prisms  weighing'  either  1  or  2  grammes  each  and 
composed  of  equal  parts  of  mercuric  chloride  and  sodium  chloride 
and  colored  red  by  an  aniline  dye.  It  likewise  introduced  the  re- 
quirement that  each  tablet  must  be  wrapped  in  black  paper  on 
which  was  printed  in  white  the  word  "  Poison." 

The  Austrian  Pharmacopoeia  (1906),  under  the  title  Pastilli 
hydrargyri  bichlorati  corrosivi,  directed  that  equal  parts  of  mercuric 
chloride  and  sodium  chloride  should  be  triturated  to  a  thorough 
mixture  and  colored  with  a  solution  of  eosin  and  compressed  into 
pastilles  weighing  2  grammes  or  1  gramme.  The  pastilles  are 
directed  to  be  dispensed  in  glass  bottles  under  a  poison  label,  and 
the  pastilles  are  to  be  singly  wrapped  in  black  paper  with  the  word 
"  Poison  "  imprinted  in  white. 

The  Swiss  Pharmacopoeia  (1907)  adopts  as  a  title  "  Hydrargy- 
rum bichloratum  compressum,"  and  as  synonym  "  Pastilli  Sub- 
limati."  The  formula  is  mercuric  chloride  666  Gm.,  sodium  chloride 
333  Gm.,  Eriocyanin  A  1  Gm.,  mixed  and  compressed  into  tablets 
weighing  37.5  eg.,  75  eg.,  and  1.5  Gm.,  and  containing  respectively 
each  25  eg.,  50  eg.,  and  1  Gm.  of  corrosive  sublimate.  It  directs 
that  each  tablet  must  be  wrapped  in  black  paper  on  which  is  printed 
in  white  the  weight  of  the  sublimate  contained,  the  word  "  Poison," 
and  a  death-head  design. 

The  British  Pharmaceutical  Codex,  in  the  first  edition  of  1907, 
and  likewise  in  the  191 1  edition,  gave  formulas  for  a  series  of  these 
tablets.  Under  the  name  of  "  Solvellse  Hydrargyri  Perchloridi, — 
Soluble  Mercuric  Chloride  Tablets,"  and  as  a  synonym  "  Antiseptic 


Am'ju<iyr'i9Pi4arm"}      Bichloride  of  Mercury  Tablets.  315 

Perchloride,  or  Corrosive  Sublimate,  Tablets,"  it  directed  a  mixture 
of  equal  parts  of  mercuric  chloride  and  sodium  chloride  colored  with 
methyl  violet  to  be  compressed  into  tablets  containing  8.75  grains  of 
the  mercuric  chloride,  so  that  one  dissolved  in  the  imperial  pint 
(20  fl.  ozs.)  of  water  will  make  a  1/10  per  cent.  (1  in  1000)  solution 
of  mercuric  chloride.  Under  the  title  "  Solvellse  Hydrargyri  Per- 
chloridi  Fortes  or  Strong  Soluble  Mercuric  Chloride  Tablets," 
a  tablet  of  the  same  percentage  of  essential  ingredients,  but  double 
the  weight,  was  directed  so  that  one  dissolved  in  20  fluidounces  of 
water  makes  1/5  per  cent.  (1  in  500)  of  mercuric  chloride.  Other 
formulas  are  given  for  a  "  mild  "  and  for  a  "  small  "  soluble  mercuric 
chloride  tablet  yielding,  when  dissolved  as  directed,  solutions  1  in 
4000  and  1  in  4500,  the  latter  being  especially  recommended  as  suit- 
able for  ophthalmic  purposes. 

The  French  Pharmacopoeia  (1908)  presents  a  new  style  of 
formula*  for  use  of  mercuric  chloride  in  antiseptic  solution.  Its 
formula  for  Papier  au  Chlorure  Mercurique  or  Charta  hydrargyri 
bichlorati  directs  that  5  Gm.  each  of  mercuric  chloride  and  sodium 
chloride  be  dissolved  in  a  sufficient  quantity  of  distilled  water  to 
obtain  a  volume  of  20  c.c.  Filter-paper  purified  by  treating  with 
water  containing  one  part  of  hydrochloric  acid  to  the  thousand, 
washing  with  pure  water  and  drying,  is  then  saturated  with  the 
mercuric  chloride  solution  so  that  each  rectangular  surface  5  cm. 
by  10  cm.  shall  imbibe  1  c.c.  of  the  solution  and  represent  25  eg.  of 
mercuric  chloride.  The  superscription,  "  Corrosive  Sublimate " 
"  twenty-five  centigrammes,"  is  directed  to  be  printed  with  indigo 
carmine,  thus  producing,  when  immersed  in  the  proper  volume  of 
water,  a  blue  solution.  The  paper  is  to  be  protected  from  light 
and  moisture  and  the  container  to  be  labelled  in  indelible  red  letters 
b  POISON." 

These  specifications  of  the  Pharmacopee  Francaise,  official  in 
that  country  since  July  17,  1908,  will  yield  a  product  essentially  the 
same  as  the  corrosive  sublimate  leaflets  now  being  made  by  an 
American  manufacturer  who  claims  originality  and  the  right  to  a 
patent  thereon  as  a  new  and  novel  invention. 

The  Italian  Pharmacopoeia  (1909)  gives  the  title  "  Pastiglie  di 
Cloruro  Mercurico  "  with  the  latin  Pastilli  bichlorureti  hydrargyri. 
Its  formula  is  mercuric  chloride  and  sodium  chloride  equal  parts 
colored  with  an  aqueous  solution  of  eosin  and  compressed  into  cir- 
cular pastilles  of  1  or  2  grammes  in  weight. 


316  Bichloride  of  Mercury  Tablets.  {^mSI'jSSl^ 

It  is  to  be  noted  that  most  of  the  foreign  pharmacopoeias  have 
simply  followed  in  their  titles  that  proposed  by  Angerer,  and  desig- 
nate these  tablets  as  pastilles.  In  the  same  pharmacopoeias  the  title 
pastilli  is  frequently  applied  to  mild  remedial  agents  dispensed  in 
the  form  of  confections  or  lozenges.  It  is  certainly  an  unfortunate 
designation  and  a  dangerous  classification  that  would  include  such 
a  toxic  form  along  with  worm  lozenges,  cough  troches,  peppermint 
drops,  etc.  It  is  still  more  to  be  regretted  that  it  has  been  proposed 
to  adopt  this  same  title  in  the  U.  S.  P.  IX.  The  use  of  the  word 
"  pastille  "  in  this  connection  is  not  in  accordance  with  the  English 
usage  of  this  word.  As  defined  in  the  dictionaries  the  word 
"pastille  "  refers  to  several  forms  of  substances  of  an  entirely  differ- 
ent character  and  dissimilar  use. 

The  Century  Dictionary  defines  pastille  or  pastil : 
"  I — A  small  roll  of  aromatic  paste,  composed  of  gum  benzoin, 
sandalwood,  spices,  charcoal  powder,  etc.,  designed  to  be  burned  as 
a  fumigator. 

"  2 — A  kind  of  sugared  confection,  usually  of  a  strong  flavor,  of 
a  round  flat  shape,  like  peppermint  drops. 

"3 — In  art:  (a)  a  thin,  round  cake  of  water  color;  (b)  the 
method  of  painting  with  water  colors  prepared  as  pastils  or  a  draw- 
ing produced  by  them. 

"  4 — In  pyrotechny  a  paper  case  filled  with  a  burning  composition, 
intended  to  cause  rotation  of  a  wheel." 

Neither  of  these  definitions  would  cover  a  mercuric  chloride 
tablet  of  the  shape  described  and  the  intended  use.  In  medicine 
and  pharmacy  this  title  had  already  been  preempted  and  used  to  a 
considerable  extent  for  medicated  confections,  and  its  adoption  for 
such  a  toxic  official  preparation  is  an  exceedingly  dangerous  experi- 
ment. It  was  probably  for  this  reason  that  the  Pharmacopoeia 
Helvetica  adopted  as  its  title  "  Hydrargyrum  bichloratum  com- 
pressum,"  and  the  British  Pharmaceutical  Codex  "  Solvellse."  The 
"  Solvellse  "  of  the  Codex  are  compressed  tablets  or  discs  intended 
to  be  dissolved  in  water  for  external  or  local  use.  The  attempt  at 
classification  here  made  is  a  step  in  the  right  direction.  The  title 
coined,  however,  does  not  indicate  the  toxic  character  and,  more- 
over, is  subject  to  the  criticism  that  it  has  the  appearance  of  an 
attempt  to  imitate  the  trade-marked  name  of  a  certain  brand  of 
tablets  extensively  used  in  England. 

The  necessity  is  for  a  distinct  title  that  will  clearly  differentiate 


Amjui°yuri9i4arm*}      Bichloride  of  Mercury  Tablets.  317 

between  the  medicinal  tablets  used  so  extensively  for  oral  adminis- 
tration and  such  poisonous  tablets  intended  for  external  use.  The 
safeguarding  of  life  is  the  first  and  principal  consideration,  and  this 
warrants  the  coining  of  a  new  title  that  shall  distinguish  the  latter 
as  a  separate  and  distinct  class.  For  this  purpose  I  propose 
Toxitabellce  as  a  distinctive  class  title,  and  as  the  official  title  for 
these  tablets,  "  Toxitabellse  Hydrargyri  Chloridi  Corrosivi,"  and  as 
the  English,  "  Poison  Tablets  of  Corrosive  Mercuric  Chloride." 

The  foreign  formulas  follow  the  formula  of  Angerer  in  directing 
equal  parts  of  mercuric  chloride  and  sodium  chloride.  The  Ameri- 
can manufacturers  generally  claim, on  their  labels  to  adhere  to  the 
Wilson  formula.  Tablets  containing  the  proportion  of  ammonium 
chloride  directed  in  this  latter  formula  are  prone  to  change  on  keep- 
ing. They  deliquesce  in  humid  atmospheres,  and  the  solubility  also  de- 
teriorates with  age.  For  these  reasons,  some  of  the  manufacturers 
have  already  substituted  sodium  chloride  for  part  of  the  ammonium 
chloride.  One  manufacturer  advises  that  he  has  found  preferable 
a  mixture  of  corrosive  sublimate  7.3  parts,  ammonium  chloride  2.7 
parts,  sodium  chloride  5  parts.  The  entire  replacement  of  the 
ammonium  chloride  by  the  sodium  chloride  will  doubtless  yield  a 
more  stable  and  soluble  tablet,  and  this  change  should  be  adopted 
in  the  pharmacopceial  formula. 

The  coloring  of  bichloride  of  mercury  antiseptic  tablets  was 
originally  proposed  not  only  to  make  them  distinct  in  color  from 
other  tablets  of  the  same  shape  and  size,  but  the  primal  idea  was 
to  obtain  a  solution  that  would  have  a  distinct  color  and  not  be 
mistaken  and  administered  for  harmless  medications  or  water.  Such 
accidents  had  occurred,  and  to  prevent  recurrence  Angerer  proposed 
as  an  additional  safeguard  that  the  solutions  should  be  colored.  It 
has  been  difficult  to  select  a  red  dye  that  would  possess  sufficient 
tinctorial  strength  so  that  only  a  minute  quantity  would  be  required 
and  at  the  same  time  be  permanent  and  not  altered  by  the  action  of 
the  chemicals  nor  fade  on  keeping.  This  problem  has  confronted 
the  manufacturers  and  has  been  the  subject  of  considerable  experi- 
mentation on  the  part  of  the  writer. 

Eosin  in  the  quantity  proposed  yields  a  tablet  that  is  distinctly 
pink,  but  when  in  solution  (1  HgCl2  in  1000)  does  not  show  a  dis- 
tinct color.  This  practical  difficulty  with  the  red  dyes,  their  variable 
shades,  and,  moreover,  the  fact  that  confections  are  frequently  of 
this  color  and  liquid  medicines  are  likewise  commonly  some  shade 


318  Bichloride  of  Mercury  Tablets.       { Am'jui°y  r*i9Pi4arm' 

of  red,  have  led  to  the  use  of  other  colors.  The  British  Pharma- 
ceutical Codex  directs  methyl  violet,  which  in  this  combination  gives 
a  blue-purple  solution.  The  Swiss  Pharmacopoeia  orders  Eriocy- 
anin  A,  the  sodium  salt  of  a  sulphonated  dye  of  the  triphenyl- 
methane-carbinol  type  that  colors  silk  and  wool  a  bright  blue  and 
is  only  slightly  affected  by  10  per  cent,  hydrochloric  acid.  The 
French  Codex  directs  indigo  carmine  for  this  purpose. 

A  number  of  the  manufacturers  are  already  giving  preference  to 
the  blue  tablets.  One  of  these  writes :  "  Green  and  red  colored 
tablets  are  not  at  all  satisfactory.  I  believe  that  you  will  agree  with 
me  that  a  sombre  blue  would  prove  the  most  desirable.  Confections 
are  made  in  red,  green,  yellow,  white,  and  every  conceivable  color, 
but  the  blue  is  not  attractive  and  therefore  would  in  all  probability 
prove  the  safest.  On  the  question  of  coloring  for  mercuric  chloride, 
Dr.  A.  G.  Rosengarten,  whose  firm  prepares  large  quantities  of 
mixed  salts  already  colored  for  the  manufacturers,  writes  me ; 

"  The  only  satisfactory  color  that  we  have  found  is  the  blue  dye, 
called  indigo  carmine.  We  have  not  yet  found  a  satisfactory  red  or 
green  dye,  but  I  can  highly  recommend  indigo  carmine  for  consistent 
results,  and  a  definite  weight  of  that  dye  added  to  a  definite  weight 
of  corrosive  sublimate  mixture  will  produce  definite  results.  I  can- 
not say  the  same  about  the  other  dyes,  and  I  think  it  will  be  most 
desirable  to  confine  the  dyes  for  corrosive  sublimate  mixture  to 
the  one  color,  blue,  and  the  one  dye,  indigo  carmine." 

My  own  experiments  confirm  these  statements  as  to  the  avail- 
ability of  indigo  carmine  for  this  purpose.  2.5  mg.  per  tablet  is  ' 
sufficient  to  color  500  c.c.  of  water  a  distinct  blue.  If  a  more 
intense  color  be  desired,  this  can  be  increased  up  to  5  mg.,  and  the 
quantity  to  be  specified  in  the  formula  for  100  tablets  should  not 
exceed  .5  Gm.  In  my  experiments  with  red  dyes,  iod-eosin  and 
alizarin  carmine  (sodium  alizarin  sulphonate)  appear  to  have  given 
the  best  results  with  the  Wilson  type,  but  the  color  of  the  solutions 
is  not  as  bright  a  red  as  might  be  desired.  With  the  Bernay"  formula 
containing  citric  acid,  methyl  orange  has  shown  the  best  results. 

The  official  tablet  should  be  adjusted  to  the  basis  of  one  tablet  to 
500  c.c.  of  water,  yielding  a  1  in  1000  solution,  instead  of  one  tablet 
to  the  pint,  as  has  been  the  custom.  This  will  necessitate  only  a 
slight  increase  in  the  weight. 


Amj«u°yri9i4arm'}       Bichloride  of  Mercury  Tablets.  319 

The  shape  to  be  adopted  for  the  official  bichloride  tablets  is  one 
of  the  questions  that  is  being  considered.  When  these  tablets  were 
introduced,  the  manufacturers  quite  naturally  used  the  moulds  that 
they  had  for  their  compressing  machines,  and  so  the  unfortunate 
mistake  was  made  of  manufacturing  these  of  the  round  or  disc 
shape ;  the  same  shape  and  sizes  as  were  used  for  innocuous  medi- 
cinal tablets  and  confections.  Fatal  accidents  have  demonstrated 
that  it  is  imperative  that  this  dangerous  practice  should  be  discon- 
tinued. Toxic  tablets  of  the  bichloride  of  mercury  antiseptic  type 
should  be  made  in  a  distinct  shape  that  has  not  been  used  for  any 
other  purpose,  and  the  use  of  such  a  shape  or  form  should  be  restricted 
by  legal  enactments*  to  such  toxic  tablets  intended  for  external  use. 

In  recent  years  the  ingenuity  of  the  American  manufacturer  has 
been  exercised  to  obtain  a  distinctive  shape  that  should  characterize 
and  distinguish  his  brand  of  "  antiseptic  tablets."  As  a  result,  we 
now  have  such  shapes  as  triangular,  diamond,  square,  cube,  key- 
stone, clover  leaf,  exploited  as  proprietary  forms  of  antiseptic 
tablets.  Every  one  of  these  shapes  has  been  commonly  used  in 
confections,  and  their  official  recognition  and  continuance  for 
bichloride  antiseptic  medication  would  be  a  repetition  of  the  original 
fatal  error  as  to  the  shape  of  such  tablets.  The  manufacturers  of 
these  shapes  are  each  clamoring  for  the  recognition  of  his  par- 
ticular shape. 

The  influence  of  these  commercial  interests  has  been  exerted  to 
prevent  legislative  action  that  would  designate  an  appropriate  shape 
or  judicial  consideration  that  would  permit  judgment  to  crystallize 
in  favor  of  an  official  shape  that  would  insure  the  greatest  amount 
of  protection  to  life.  After  all,  the  question  of  safety  first  is  the 
paramount  question. 

Of  all  the  proposals  for  a  shape  for  bichloride  of  mercury  tablets, 
the  coffin  shape  suggested  by  Mr.  F.  M.  Apple  in  his  paper  before 
the  Pennsylvania  Pharmaceutical  Association  seems  to  be  best.  This 
has  already  been  adopted  by  at  least  four  manufacturers,  and  its 
general  adoption  has  only  been  prevented  by  the  commercial  in- 
terests back  of  other  designs.  Commercial  instincts  and  financial 
advantages,  and  not  the  broad  humanitarian  principle  of  what  is 
best  to  protect  life,  have  been  the  causes  actuating  the  opposition  to 
legislation  and  to  official  recognition  of  the  best  suggestion  yet 
offered. 

The  German  Pharmacopoeia  has  been  quoted  as  an  authority 


320  Bichloride  of  Mercury  Tablets.       { Am-  ^Jj™- 

to  be  followed  in  fixing  the  U.  S.  P.  standard.  I  believe  that  we 
should  appropriate  from  the  foreign  pharmacopoeias  all  that  our 
experience  and  judgment  prove  to  be  correct  and  in  accordance  with 
American  practice.  In  this  instance  I  cannot  approve  of  following 
the  dictum  of  the  German  Pharmacopoeia.  I  have  here  a  sample 
of  the  official  German  corrosive  sublimate  tablets  that  have  been  in 
my  possession  since  last  March.  You  will  observe,  first,  that  these 
are  not  uniform  in  color  and  that  fading  has  commenced  to  take 
place.  Secondly,  the  shape  is  in  conformity  with  that  of  the  Ph.  Gr., 
twice  as  long  as  broad,  and  the  manufacturer,  to  show  this  and 
possibly  to  permit  of  economy  in  using  only  half  a  tablet  at  a  time, 
has  made  them  with  a  ridge  across  the  centre.  This  resembles  forms 
of  the  pink  linked  phenolphthalein  and  other  proprietary  laxative 
wafers  that  are  so  extensively  used  in  this  country.  It  would  be 
difficult  to  conceive  of  a  more  dangerous  experiment  than  to  officially 
recognize  such  a  shape  for  bichloride  tablets.  It  would  be  on  a  par 
with  the  adoption  of  the  Italian  pharmacopceial  standard  of  the 
round  tablet  which  we  are  now  ready  to  condemn.  There  is  no 
uniformity  in  the  European  pharmacopoeias  on  this  formula,  and 
so  the  argument  for  adopting  an  international  standard  falls  flat. 
Thirdly,  the  solution,  when  made  of  a  strength  of  I  to  iooo,  as 
commonly  used,  is  so  delicate  a  pink  tint  as  to  be  barely  perceptible. 

So  far  as  I  know,  no  American  manufacturer  has  yet  placed  on 
the  market  a  bichloride  of  mercury  tablet  copied  after  that  of  the 
German  Pharmacopoeia.  As  this  formula  has  been  published  for 
more  than  fourteen  years,  this  is  noteworthy  and  may  be  construed 
as  an  evidence  of  the  good  judgment  of  our  manufacturers.  To 
now  insist  that  the  U.  S.  Pharmacopoeia  must  adopt  and  make  legal 
a  shape  that  has  not  met  favor  in  American  practice  is  a  unique 
proposition  that  lacks  the  popular  approval  that  is  essential  to  its 
effectiveness. 

The  importance  of  throwing  every  safeguard  possible  around  the 
sale  and  handling  of  such  poisonous  substances  is  now  thoroughly 
recognized.  The  newspapers  have  given  wide  publicity  to  the 
deaths,  either  suicidal  or  accidental,  occurring  from  bichloride 
tablets.  The  evils  resulting  from  the  overzealous  newspaper  which 
gives  its  readers  all  the  details  of  the  method  by  which  some  poor 
unfortunate  has  gone  on  the  long  voyage,  have  been  discussed  and 
decried,  yet,  nevertheless,  it  continues  its  course  with  little  or  no 
abatement. 


Am  j.u°yri9i4.ann" }       Bichloride  of  Mercury  Tablets.  321 

A  number  of  State  legislatures  in  session  during  the  past  year 
have  had  under  consideration  acts  that  would  restrict  the  handling 
of  such  poison  tablets  and  define  their  shape,  color,  and  label,  and 
further  prohibit  the  use  of  the  prescribed  shape  for  any  other 
purpose.  There  are  at  least  three  bills  on  the  same  subject  now 
pending  in  Congress.  It  is  certain  that  we  may  expect  legislation 
before  long  on  this  entire  matter,  and  it  is  eminently  proper  that 
the  drug  trade  should  take  an  active  interest  in  solving  a  question 
of  public  safety  that  is  so  closely  associated  with  our  business.  Un- 
fortunately, the  attitude  assumed  by  some  of  the  druggists  is  that 
of  thoughtless  indifference.  The  argument  advanced  by  others  is 
that  such  legislation  is  only  a  passing  sentimental  fad  and  that  it  can 
have  no  influence  on  the  protection  of  life.  This  is  so  fallacious  that 
it  can  not  long  continue  to  prevent  legislation. 

It  was  never  expected  that  any  legislation  would  prevent  a  person 
of  morbid  mind  from  committing  suicide.  This  is  not  the  purpose 
of  the  proposed  legislative  enactments,  but  it  is  contended  that  in 
prescribing  a  distinctive  shape  for  these  poison  tablets  they  could 
under  no  circumstances  be  mistaken,  either  in  the  day  or  night,  for 
harmless  medications.  If  a  distinctive  shape  had  been  supplied  the 
Macon,  Ga.,  banker  and  the  Brooklyn  business  man,  whose  deaths 
beyond  question  were  accidental  poisonings,  at  least  these  lives  could 
have  been  spared. 

The  necessity  for  a  distinctive  shape  for  bichloride  of  mercury 
tablets  is  well  shown  by  the  compilation  appearing  in  Public  Health 
Report  No.  46,  by  Martin  I.  Wilbert,  of  the  United  States  Public 
Health  Service.  In  this  compilation  Mr.  Wilbert  shows  that  at 
that  time,  in  the  current  price-lists  of  five  leading  pharmaceutical 
manufacturers,  there  were  sixteen  different  formulas  and  varying 
sizes  of  poison  bichloride  tablets,  five  different  shapes,  five  different 
colors,  and  only  three  out  of  the  sixteen  were  then  made  of  any 
other  shape  than  the  ordinary  round  tablets  used  for  medicine,  such 
as  headache  and  cold  tablets.  Could  any  stronger  evidence  of  the 
necessity  for  restrictive  legislation  and  a  distinctive  shape  for  these 
poison  tablets  be  presented  than  this  compilation  in  a  Government 
bulletin,  which  shows  the  present  dangerous  and  unsatisfactory 
method  of  marketing  these  tablets  ? 

The  influence  of  certain  manufacturers  on  proposed  legislation  is 
shown  in  the  act  passed  by  the  last  session  of  the  Maryland  legis- 
lature.   Instead  of  specifying  in  the  act  a  distinctive  shape  or  color, 


322 


Liquid  Petrolatum. 


Am.  Jour.  Pharm. 
July,  1914. 


the  value  of  the  legislation  is  largely  nullified  by  the  amended  form 
in  which  the  bill  was  passed.  This  law  provides  that  "  Tablets  con- 
taining more  than  i/io  grain  of  mercury  bichloride  must  be  of 
either  triangular,  diamond,  square,  oblong,  or  other  irregular  shape, 
and  their  color  must  be  either  blue,  purple,  or  green,  with  the  word 
'  Poison  '  imprinted  or  embossed  on  each  tablet.  Further,  these 
tablets  can  only  be  sold,  dispensed,  or  given  away  in  bottles  upon  one 
side  of  which  the  word  '  Poison  '  has  been  blown,  and  when  a  label 
with  the  word  '  Poison  '  is  placed  on  the  face  of  the  bottle." 

The  restrictions  regarding  the  package  and  labelling  are  such  as 
are  commonly  employed  by  all  of  the  manufacturers,  but  the  very 
needed  protection  to  the  consumer  has  been  lost  sight  of  by  the  over- 
powering commercial  spirit  that  prevented  the  selection  of  a  dis- 
tinctive shape  for  the  tablets.  Any  one  of  a  number  of  shapes  is 
equivalent  to  no  shape,  and  the  very  indefiniteness  of  the  act  as 
passed  through  the  influence  of  the  manufacturers  destroys  its  value 
as  a  measure  for  the  safety  of  the  public. 


LIQUID  PETROLATUM  OR  "  RUSSIAN  MINERAL  OIL." 

Report  of  the  Council  on  Pharmacy  and  Chemistry. 

The  following  report  was  submitted  to  the  Council  by  a  referee 
and  publication  authorized. 

W.  A.  Puckner,  Secretary. 

Petroleum  has  been  in  use  as  a  medicine  from  time  immemorial. 
It  was  known  to  Herodotus  400  years  before  Christ,  and  is  mentioned 
by  Plutarch,  Dioscorides,  Pliny,  and  other  early  writers.  It  was 
extensively  used  by  the  Arabians  and  evidently  played  an  important 
part  in  the  practice  of  medicine  in  India,  being  known  to  the  Benga- 
lese  as  Muthe  Katel.  The  raw  product  was  the  substance  used  in 
earlier  times  and  differed  much  in  character  and  composition,  as 
obtained  from  different  sources. 

As  an  internal  remedy  it  was  early  employed  in  chronic 
pulmonary  affections,  in  obstinate  skin  diseases,  in  rheumatism,  and 
for  the  expelling  of  tapeworms.  It  was  extensively  used  for  these 
several  purposes  in  France  under  the  name  "  Oleum  Gabianum  "  and 
in  North  America  as  "  Seneka  oil."  The  internal  use  of  the  refined 
product  may  be  traced  to  a  patent  granted  to  Robert  A.  Chesebrough, 


^Jufy,ri9uarm'}  Liquid  Petrolatum,  323 

of  New  York,  in  June,  1872,  for  the  manufacture  of  a  "  new  and 
useful  product  from  petroleum,  named  vaseline."  This  name  was 
originally  applied  only  to  a  semisolid  preparation,  but  later  a  liquid 
product  known  as  liquid  vaseline  was  marketed  and  for  a  time  ex- 
ploited as  a  cure  for  coughs,  colds,  consumption,  and  a  number  of 
other  diseases  and  conditions. 

The  liquid  petrolatum  has  since  become  known  under  a  variety 
of  names,  proprietary  and  otherwise,  in  addition  to  being  used  as  a 
substitute  or  an  adulterant  for  other,  more  costly,  fats  and  oils. 
Some  of  the  names  applied  to  the  product  are : 


Adepsine  oil 

Neutralol 

Amilee 

Olo 

Atoleine 

Paraffin  oil 

Atolin 

Paroline 

Blandine 

Petro 

Crysmalin 

Petrolax 

Deeline 

Petrolia 

Glyco 

Petrolol 

Glycoline 

Petronol 

Glymol 

Petrosio 

Heavy  petroleum  oil 

Rock  oil 

Liquid  albolene 

Russian  liquid  petrolatum 

Liquid  cosmoline 

Russian  mineral  oil 

Liquid  fossiline 

Russian  paraffin  oil 

Liquid  geoline 

Russol 

Liquid  paraffin 

Saxol 

Liquid  petrolatum 

Terralbolia 

Liquid  saxoline 

Terraline 

Liquid  vaseline 

Usoline 

Mineral  glycerin 

Water-white  mineral  oil 

Mineral  oil 

White  paraffin  oil 

A  preparation  similar  to  that  official  in  the  Pharmacopoeia  of 
the  United  States  as  liquid  petrolatum  has  been  included  in  many, 
if  not  all,  of  the  foreign  pharmacopoeias,  the  official  title  under  which 
this  preparation  is  recognized  being  as  follows : 

Petrolatum  liquidum,  U.  S.  Pharmacopoeia ;  Paraffinum  liquidum, 
pharmacopoeias  of  Great  Britain,  Germany,  the  Netherlands,  Japan, 
Belgium,  Austria,  Denmark,  Switzerland,  Sweden,  Servia,  Italy, 
Hungary  and  Russia ;  Oleum  Paraffinse,  Spanish  Pharmacopoeia ; 
Vaselinum  liquidum,  French  Pharmacopoeia,  and  Oleum  vaselini 
(as  a  synonym),  pharmacopoeias  of  Denmark  and  Russia. 


324 


Liquid  Petrolatum. 


I  Am.  Jour.  Pharm. 
I       July,  1914. 


The  requirements  of  the  several  pharmacopoeias  differ  somewhat, 
and  the  specific  gravity  as  given  is  as  follows : 


For  pharmaceutical  purposes,  liquid  petrolatum  may  be  divided 
into  two  grades,  the  lighter  or  more  limpid  oil,  used  extensively  as  a 
vehicle  for  oil  sprays,  and  the  heavier,  more  viscid  oil  generally 
recognized  in  European  pharmacopoeias  and  used  as  an  ingredient 
of  ointments  and  more  recently  as  a  remedy  in  the  treatment  of 
intestinal  stasis. 

Under  petrolatum  liquidum  the  U.  S.  P.  recognizes  a  mixture  of 
hydrocarbons,  chiefly  of  the  methane  series,  which  occurs  as  a  color- 
less or  very  slightly  yellowish,  oily,  transparent  liquid  without  odor  or 
taste  and  having  a  specific  gravity  of  about  0.870  to  0.940  at  25 0  C. 
For  the  U.  S.  P.  IX,  it  is  proposed  to  change  this  requirement  some- 
what so  as  to  have  it  apply  to  a  transparent  liquid  free  from  fluores- 
cence, without  odor  or  taste  and  having  a  specific  gravity  of  from 
0.845  to  °-94P  at  25 0  C. 

Such  a  requirement  would  include  all  of  the  available  paraffin 
oils,  irrespective  of  origin.  The  now  commonly  available  commercial 
liquid  petrolatum,  used  for  pharmaceutical  purposes,  is  practically 
colorless  and  all  of  the  better  grades  are  free  from  odor  or  taste. 
The  specific  gravity  varies  from  0.855  to  0.895.  The  lighter  oils, 
having  a  specific  gravity  of  from  0.860  to  0.870,  are  usually  preferred 
in  the  making  of  oil  sprays  or  solutions  of  substances  to  be  used  as 


U.  S.  P.  VIII,  1905   

Ph.  Brit.  IV,  1895   

B.  P.  C.  II,  191 1,  usually  

Ph.  Germ.  V,  1910,  at  least  . . 

Ph.  Ross,  VI,  1910   

Ph.  Hung.  Ill,  1909   

Ph.  Ital.  Ill,  1909   

Ph.  Fr.  V,  1908,  about   

Ph.  Serb.  II,  1908,  about 

Ph.  Svec.  IX,  1908   

Ph.  Helv.  IV,  1907   

Ph.  Dan.  VII,  1907,  at  least  . . 
Ph.  Austr.  VIII,  1906,  at  least 
Ph.  Belg.  Ill,  1906,  not  below  . 

Ph.  Japon.  Ill,  1906   

Ph.  Ndl.  IV,  1905,  not  below 
Ph.  Hisp.  VII,  1905   


0.870  to  0.940  at  25 0 
0.885  to  0.890  at  1 5. 50 
0.875  or  lower  at  150 
0.885  at  15° 

0.880  to  0.885  at  15° 
0.88  to  0.89  at  1 50 
0.875  to  0.890  at  150 
0.875  at  150 

0.880  at  15° 

0.88  to  0.90  at  150 
0.880  to  0.885  at  15° 
0.880  at  15° 

0.880  at  15° 

0.880  at  1 5° 

0.875  to  0.945  at  150 
0.860  at  1 5° 

0.840  at  150 


Am.  Jour.  Pharm. 
July,  1914. 


Liquid  Petrolatum. 


325 


local  applications.  The  product  having"  a  specific  gravity  above 
0.875  evidently  contains  a  considerable  amount  of  dissolved  solid 
paraffin  which  separates  out  at  temperatures  at  or  below  o°  C,  but 
readily  dissolves  again  at  temperatures  above  io°  C. 

There  is  considerable  difference  in  the  chemical  composition  of 
the  paraffin  oils  obtained  from  various  sources.  The  American  oil 
consists  largely  of  hydrocarbons  of  the  methane  series,  while  the 
Russian  oil  contains  naphthenes  or  hydrocarbons  of  the  benzene 
series,  having  the  empirical  composition  of  ethylene  (CnH2n),  which 
may  be  considered  as  hydrogenated  aromatic  hydrocarbons,  though 
they  behave  with  reagents  very  much  in  the  same  way  as  do  the 
hydrocarbons  of  the  methane  series. 

Mineral  oils  with  a  naphthene  base  are  best  suited  for  making 
white  petrolatum,  and  at  the  present  time  the  production  of  the 
colorless  water-white  liquid  petrolatum  appears  to  be  confined  largely 
or  almost  exclusively  to  the  crude  product  of  the  Baku  district  of 
Russia,  though  it  is  asserted  that  it  is  now  also  made  from  the 
Hanover  (Germany)  crude  oil  and  that  some  is  being  produced  by 
"  cracking  "  the  white  solid  paraffin. 

It  is  also  said  that  the  American  oil  can  be  made  water  white,  but 
that  it  is  not  being  so  produced  at  present  for  economic  reasons ;  the 
yellowish  oil,  free  from  fluorescence,  having  a  very  wide  sale,  both 
as  a  lubricant  and  as  a  substitute  for  lard  oil  and  other  of  the  more 
costly  lubricating  oils. 

From  a  pharmaceutical  point  of  view  it  would  appear  important 
to  note  the  physical  characteristics  of  the  oil  and  to  insist  on  absence 
of  color,  absence  of  odor  and  taste,  absence  of  acid  and  of  alkali 
and  a  specific  gravity  in  harmony  with  the  purposes  for  which  the 
oil  is  to  be  used. 

During  the  past  year  or  two  liquid  petrolatum  has  attracted 
considerable  attention  as  a  remedy  in  the  treatment  of  intestinal 
stasis  or  chronic  constipation,  the  practice  of  using  it  having  been 
developed  largely  through  its  recommendation  by  Sir  W.  Arbuthnot 
Lane  and  his  associates.  This  use  of  liquid  petrolatum  and  of 
petrolatum  products  generally  is  by  no  means  novel.  N.  A. 
Randolph,1  of  Philadelphia,  was  among  the  first  to  suggest  its  use 
for  this  purpose  in  an  article  published  in  1885.   Randolph  also  ap- 


1  Randolph,  N.  A. :  Therap.  Gas.,  1885,  ix,  732. 


326 


Liquid  Petrolatum. 


( Am.  Jour.  Pharm. 
\       July,  1914. 


pears  to  have  been  the  first  to  experiment  with  petrolatum  and  to 
determine  its  non-absorbability  from  the  intestinal  tract.  In  an 
article  2  in  1884  he  concludes  that  "  pure  petrolatum  while  entirely 
unirritating  to  the  digestive  tract  is  valueless  as  a  foodstuff." 

The  experiments  recorded  by  Randolph  were  evidently  prompted 
by  the  fact  that  vaseline  and  a  number  of  imitation  products  then  on 
the  market  were  being  sold  as  substitutes  for  lard  and  butter,  and 
opinions  regarding  the  food  value  of  petroleum  products  appear  to 
have  differed  very  materially.  Following  the  experiments  of 
Randolph,  Robert  Hutchison  in  1899  made  a  series  of  experiments 
to  demonstrate  that  petroleum,  petrolatum,  paraffin  and  related  prod- 
ucts were  absolutely  unassailable  by  any  of  the  digestive  fluids, 
despite  the  "large  vogue  that  had  of  late  years  been  given  to  various 
petroleum  emulsions,  chiefly  by  ingenious  and  unterrified  advertis- 
ing." He  came  to  practically  the  same  conclusions  arrived  at  by 
Randolph  fifteen  years  earlier  and  pointed  out  that  "  liquid  paraffin 
in  one  sense  may  be  regarded  as  an  artificial  intestinal  mucus  and 
might  in  that  way  have  some  value  on  certain  forms  of  constipation." 

William  Dufifield  Robinson  3  reports  on  the  use  of  a  perfectly 
refined  colorless  and  odorless  petrolatum,  supposedly  of  American 
origin.  He  was  able  to  show  that  all  of  the  product  passed  un- 
changed through  the  intestinal  tract  and  could  be  regained  from  the 
faeces.  In  his  conclusions  he  expressed  the  belief  that  the  effect 
of  the  administration  of  these  petroleum  products  is  far  more  than 
as  a  simple  intestinal  lubricant.  In  over  fifty  selected  cases  in  which 
nutrition,  digestion  and  body-weight  were  impaired,  and  the  purest 
oil  administered  in  1-  or  2-dram  doses  each  day  for  a  period  of 
from  four  to  six  months,  there  was  in  every  instance  an  improvement 
of  weight,  health  and  feeling  of  well-being.  The  administration 
of  refined  paraffin  oil  gave  no  discomfort  in  any  instance,  even  in 
cases  in  which  nearly  a  pint  was  given  in  a  few  hours. 

William  Ewart  4  suggests  liquid  paraffin  as  a  safe  agent  for  the 
local  treatment  of  the  lesions  in  typhoid  fever.  He  says  in  part: 
"  Mineral  oil,  such  as  petrolatum  or  paraffin,  is  neither  absorbed 
nor  dissolved ;  therefore,  after  all  absorbable  ingestions  are  taken 
up  by  the  lacteals,  it  will  still  remain  in  the  bowel.    In  this  way  pure 


2  Randolph,  N.  A.:  Proc.  Acad.  Nat.  Sc.,  Philadelphia,  1884,  p.  281. 

3  Robinson :  William  Duffield  :  Med.  News,  1900,  lxxvii,  56. 

4  Ewart,  William  :  Brit.  Med.  Jour.,  1902,  ii,  1505. 


Am'jui7ri«Ji4arm' }  Liquid  Petrolatum.  327 

liquid  paraffin  is  valuable,  precisely  because  it  is  inert ;  moreover, 
it  might  some  day,  perhaps,  be  made  the  vehicle  for  effective  topical 
remedies." 

A.  D.  Schmidt 5  quotes  Stubenrath  as  having  given  liquid  paraffin 
in  the  treatment  of  chronic  constipation,  and  he  himself  gave  as 
much  as  20  gm,  of  liquid  paraffin  to  adults  without  observing  any 
injurious  effect  whatever.  He  says,  "  As  a  result  of  the  administra- 
tion of  liquid  paraffin,  the  faeces  are  softened  considerably  and  are 
found  under  the  microscope  to  contain  numerous  minute  globules 
of  paraffin."  He  was,  however,  unable  to  recover  from  the  faeces 
the  entire  quantity  of  paraffin  administered  and  believes  that  a 
certain  portion  of  it,  probably  the  fractions  with  a  low  boiling-point, 
are  absorbed  or  possibly  oxidized  in  the  organism. 

Maurice  Vejux  Tyrode  0  also  refers  to  the  use  of  liquid  petroleum 
in  the  treatment  of  constipation. 

Sir  F.  Arbuthnot  Lane  in  his  recommendations  of  liquid  petrola- 
tum calls  it  an  ideal  remedy  for  stasis,  but  cautions  against  the  use 
of  the  lighter  oil  as  extensively  prescribed  in  this  country  as  a 
vehicle  for  sprays  in  nose  and  throat  work. 

Paraffin  oil  is  not  absorbed  from  the  alimentary  tract  and  so  far 
as  known  exerts  no  deleterious  influence.  It  is  usually  given  in 
quantities  of  from  10  to  20  c.c.  half  an  hour  or  an  hour  before  meals 
or  in  larger  doses,  from  30  to  50  c.c,  at  one  time  on  retiring.  From 
available  evidence  it  appears  that  comparatively  huge  doses  may  be 
administered  without  the  production  of  any  untoward  results.  Ac- 
cording to  many  observers,  liquid  paraffin  should  not  be  given  with 
or  after  meals  because  of  the  inhibiting  influence  that  it  may  have 
on  the  digestion  of  food.  It  is  not  soluble  in  water  or  the  ordinary 
solvents  and  therefore  cannot  be  diluted.  The  denser  oils  are  pref- 
erably slightly  warmed  or  drunk  with  warm  water  so  as  to  obviate 
the  disagreeable  slimy  sensation  that  persists  when  taken  cold. 

Volatile  oils  may  be  used  in  moderate  amounts  to  give  a  dis- 
tinctive taste  to  the  otherwise  rather  insipidly  tasteless  paraffin  oil. 
Among  the  more  desirable  oils  to  be  used  for  this  purpose  would  be 
oil  of  nepnermint,  oil  of  cinnamon,  oil  of  betula  or  methyl  salicylate 
and  oil  of  cloves.  From  2  to  10  drops  of  any  of  these  oils  can  be 
added  to  a  pint  of  the  oil.    When  larger  doses  of  the  oil  are  to  be 


5  Schmidt,  A.  D. :  Milnchcn.  mcd.  Wchnschr.,  1005,  Hi,  T907. 

8  Tyrode,  Maurice  Vejux:  Boston  Mcd.  and  Surg,  Jour.,  1010,  clxii,  673, 


328 


Liquid  Petrolatum. 


J  Am.  Jour.  Pharm. 
\     July,  1914. 


given  at  one  time,  it  would,  of  course,  be  advisable  to  use  a  com- 
paratively smaller  quantity  of  the  volatile  oil  as  a  flavor.7 

From  the  foregoing  it  would  appear  that  apart  from  the 
Pharmacopoeia  of  the  United  States,  practically  all  other  known 
pharmacopoeias  describe  a  water-white  mineral  oil  under  the  title 
"  Paraffinum  Liquidum  "  or  "  Liquid  Paraffin  "  as  a  colorless,  odor- 
less, tasteless,  non-fluorescent,  oily  liquid,  free  from  acids,  alkalies 
and  organic  impurities.  As  explained  before,  the  specific  gravity  of 
the  preparation  as  recognized  in  other  countries  and  as  offered  on 
the  American  market  at  the  present  time  varies  considerably,  and 
there  appears  to  be  some  difference  of  opinion  as  to  the  exact  nature 
of  the  product  that  is  preferable  for  use  for  different  purposes. 
This  matter  requires  further  investigation. 

Since  the  definition  of  liquid  petrolatum  in  the  U.  9.  Pharma- 
copoeia permits  the  use  of  fluorescent  products  of  widely  varying 
specific  gravities,  it  is  recommended  that  physicians  who  desire  the 
water-white  non-fluorescent  (Russian)  mineral  oil  should  use  the 
term  "  Petrolatum  Liquidum,  Grave,"  or  "  Paraffinum  Liquidum,  B. 
P.,"  if  the  heavy  product  recommended  by  Lane  is  desired,  and  "  Pet- 
rolatum Liquidum,  Leve,"  if  the  light  varieties  are  required.  It  is 
further  recommended  that  under  the  foregoing  names  manufacturers 
and  pharmacists  be  requested  to  dispense  the  products,  in  accord- 
ance with  the  following  descriptions : 

Petrolatum  Liquidum,  Grave. — Heavy  (Russian)  Liquid  Pet- 
rolatum.— Paraffinum  Liquidum,  B.  P.,  liquid  paraffin. — A  trans- 
parent, colorless,  tasteless,  non-fluorescent,  oily  liquid,  odorless  when 
cold  but  giving  off  a  faint  petroleum  odor  on  heating.   This  prepara- 

7  In  addition  to  the  articles  referred  to  in  the  preceding  footnotes,  the 
following  are  of  interest  in  connection  with  this  subject: 
Editorial,  Therap.  Gaz:,  1885,  ix,  353. 
Junker,  F.  A.:  Med.  Record,  London,  1885,  xiii,  506. 
Editorial,  Med.  News,  1886,  xlviii,  105. 
Dunbar  :  Deutsch.  med.  Wchnschr.,  1896,  xxii,  33. 

Stubenrath,  Franz  Casimir :  Munchen.  med.  Wchnschr.,  1897,  xliv,  639. 

London  Letter,  Med.  News,  1899,  lxxiv,  504. 

Hutchison,  Robert :  Brit.  Med.  lour.,  1899,  i,  724. 

Schlesinger,  E.  G. :  Boston  Med.  and  Surg.  lour.,  1913,  clxix,  14. 

Lane,  W.  Arbuthnot :  Brit.  Med.  Jour.,  1913,  ii,  1126;  Proc.  Roy.  Soc. 
Med.,  1913,  vi,  49;  Surg.,  Gynec.  and  Obst,  1913,  xvi,  No.  6. 

Jordan,  Alfred  C. :  Practitioner,  London,  February,  1913. 

Chrysospathes,  J.  G. :  Zentralbl.  f.  Chir.,  1913,  No.  45 ;  abstr.,  The  Jour- 
nal A.  M.  A.,  Dec.  13,  1913,  p.  2201. 


Am"j^y^i9i4arm'}    Philadelphia  College  of  Pharmacy.  329 

tion  should  correspond  to  the  requirements  of  the  British  Pharma- 
copoeia for  liquid  paraffin  and  have  a  specific  gravity  of  about  0.885 
to  0.890  at  150  C.  It  is  insoluble  in  water  or  alcohol,  but  soluble  in 
boiling  absolute  alcohol  and  readily  soluble  in  ether,  choloroform, 
carbon  disulphide,  petroleum  benzin,  benzene,  and  fixed  and  vola- 
tile oils.  It  serves  as  a  solvent  for  volatile  oils  and  related  sub- 
stances like  camphor,  menthol  and  thymol. 

This  is  the  type  of  preparation  used  by  Sir  W.  Arbuthnot  Lane, 
and  his  associates  for  internal  administration.  It  is  also  used  as  a. 
basis  for  ointments  and  salves  and  as  a  local  application  to  wounds, 
ulcers  and  in  certain  forms  of  skin  diseases  in  which  a  simple  pro- 
tective is  desired. 

Petrolatum  Liquidum,  Leve. — Light  (Russian)  Liquid  Petro- 
latum.— A  transparent,  colorless,  tasteless,  non-fluorescent,  oily 
liquid,  odorless  when  cold,  but  giving  off  a  faint  petroleum  odor  on 
heating.  In  other  respects  this  preparation  should  correspond  to 
the  pharmacopoeial  tests  for  liquid  petrolatum  and  have  a  specific 
gravity  of  about  0.860  to  0.875  at  I5°  C.  Like  the  heavy  variety 
of  liquid  petrolatum,  it  is  insoluble  in  water  and  alcohol,  but  soluble 
in  boiling  absolute  alcohol  and  readily  soluble  in  ether,  chloroform, 
carbon  disulphide,  petroleum  benzin,  benzene  and  fixed  and  volatile 
oils.  It  serves  as  a  solvent  for  volatile  oils  and  related  substances 
like  camphor,  menthol  and  thymol. 

This  is  a  type  of  preparation  extensively  used  as  a  vehicle  for 
the  oily  sprays  in  nose  and  throat  work.  It  is  also  being  used  as  one 
of  the  constituents  in  the  now  popular  paraffin  oil  cold  cream  and 
has  been  used  to  some  extent  for  internal  administration  in  the 
treatment  of  chronic  stasis.  Being  more  limpid  than  the  preparation 
preferred  by  Lane,  it  is  more  readily  taken,  though  greater  care  must 
be  exercised  in  securing  a  sample  devoid  of  the  lighter  fractions  of 
petroleum  distillates. 


PHILADELPHIA  COLLEGE  OF  PHARMACY. 

NINETY-THIRD  ANNUAL  COMMENCEMENT. 

The  commencement  exercises  on  Thursday,  June  18th,  brought 
to  a  close  one  of  the  most  successful  commencement  weeks  in  the 
history  of  the  Philadelphia  College  of  Pharmacy.  A  very  large 
number  of  the  alumni  visited  the  college  and  attended  the  various 
functions.    The  Baccalaureate  services  were  held  at  the  Church  of 


33o 


Philadelphia  College  of  Pharmacy,  j 


Am.  Jour.  Pnarm. 
July,  1914. 


St.  Luke  and  the  Epiphany,  the  Rev.  David  M.  Steele  delivering 
an  unusually  inspiring  sermon.  On  Monday  evening  the  Faculty 
gave  their  annual  banquet  to  the  graduating  class  in  the  College 
Auditorium.  This  is  always  a  very  interesting  occasion,  in  that  it 
brings  together  the  Faculty  and  members  of  the  graduating  class  in 
a  very  close  relation,  enabling  them  to  discuss  not  only  their 
experiences  but  some  of  the  larger  questions  of  life. 

Tuesday  was  Alumni  Day,  the  Association  holding  its  annual 
meeting  in  the  afternoon,  and  in  the  evening  giving  a  reception  to 
the  members  of  the  graduating  class,  in  addition  to  the  awards  of 
the  alumni  prizes  and  a  very  excellent  musical  program.  Prof. 
Henry  Kraemer  gave  an  address,  in  which  he  read  the  class  oration 
which  he  had  delivered  twenty-five  years  ago,  at  the  time  of  his 
graduation  from  this  College.  The  annual  alumni  banquet,  which 
was  held  at  the  Hotel  Walton  on  Wednesday  evening,  was  very 
largely  attended  and  was  characterized  by  magnificent  alumni  and 
college  spirit.  The  responses  by  the  various  representatives  of  the 
classes  ending  in  4's  and  9's  showed  that  the  movement  to  mark 
the  centennial  of  the  College  and  raise  $500,000  for  new  site,  new 
buildings,  and  additional  equipment  would  receive  the  hearty 
cooperation  of  the  alumni. 

The  commencement  on  Thursday  evening  at  the  Academy  of 
Music  marked  the  climax  of  the  week's  celebration.  The  fea- 
ture of  the  evening  was  the  presence  of  the  Governor  of  Penn- 
sylvania, Hon.  John  K.  Tener,  who  delivered  a  brief  but  very 
appropriate  address'to  the  members  of  the  graduating  class  and  their 
friends  assembled.  The  opening  prayer  was  made  by  Rev.  W.  Quay 
Rosselle,  of  Philadelphia,  after  which  the  degrees  were  conferred 
by  President  Howard  B.  French. 

The  title  of  Master  in  Pharmacy  (Ph.M.) —  In  Course — was  con- 
ferred on  Professor  Edwin  L.  Newcomb,  P.D.,  of  the  University  of 
Minnesota. 

The  following  are  the  names  of  those  receiving  the  degree  of 
Doctor  in  Pharmacy  (P.D),  together  with  the  subjects  of  their 
graduating  theses : 


Name 


Thesis 


Ankrum,  Samuel  Martin. 

Balliet,  Woods  D  

Berryman,  Clarence  Haco 


Acetone   

Serums  and  Vaccines   

The  Presence  of  Arsenic  in  Tin 
Foil  


Pennsylvania 
Pennsylvania 


New  Jersey 


Am'juTy!"'i9i4arm"}     Philadelphia  College  of  Pharmacy.  331 

Name  Thesis 
Biren,  Samuel   Show  Card  Writing,  Advertising 

and  Displaying   Austria 

Botdorf,  Joseph  Franklin  . . .  .Kaolinum   Pennsylvania 

Boyd,  William  Merton   Improved  Methods  of  Preparing 

some    U.    S.    P.    and    N.  F. 

Preparations   Pennsylvania 

Burke,  John  Joseph   Cork:  Its  Origin  and  Use  New  Jersey 

Cahan,  Samuel  Sapo  Mollis   Russia 

Cameron,  Ernest  Clifford  ....  Production  of  Cacao  Pennsylvania 

Cantner,  Paul  Clifford   Acidum  Hydriodicum  Dilutum ..  Pennsylvania 

Carr,  Edmund  Eugene   Petroselini  Fructus   Utah 

Coble,  Paul  Daniel   Ammonium  Hypophosphite  Pennsylvania 

Cohen,  Louis  Pharmacy  in  Ireland   Pennsylvania 

Collins,  John  Edmund  Sapo    Mollis    ex    Oleo  Gossypii 

Seminis   Pennsylvania 

Comber,  Gertrude  Agnes  [P.C.]  Magnesium  Oxide  ..Pennsylvania 

Coolbaugh,  Leonard  Ellsworth  Cudbear   New  York 

Craft,  William  Wheeler  The  Typho-Bacterins   District  of 

Columbia 

Davidson,  Wilmer  Paul  Tincture  of  Iodine   Pennsylvania 

Dickson,  Thomas  Young  Ground  Flaxseed  Pennsylvania 

Dils,  Chauncey  Lloyd   Manufacture  of  Window  Glass. .  Pennsylvania 

Dougherty,  Christ  Patrick,  Jr.  Aromatic  Spirit  of  Ammonia.  ...  Pennsylvania 

Duvoisin,  Agnes,  [P.C.]  Plasters  and  their  Spreading.  ...  Pennsylvania 

Edwards,  Harold  Powell  Elixir  Ferri,  Quininse  et  Strych- 

ninse  Phosphatum   Maine 

Eldredge,  William  Payson  Phenolsulphonaphthalein  :  Func- 
tional Test —   Pennsylvania 

Epstein,  Meyer  Charles  Chocolate  and  Cocoa   Pennsylvania 

Fiscel,  John  Arthur  Sapo  Mollis   Pennsylvania 

Fitzsimmons,  William  Henry.  .Crude  Petroleum   Pennsylvania 

Flanagan,  Clark  Harrison  Compound  Syrup  of  Hypophos- 

phites,  U.  S.  P  New  York 

Fox,  James  Andrew  Specifications  for  Portland  Ce- 

j       ment   Pennsylvania 

Frank,  William  Reuben  Incandescent  Gas  Lighting   Pennsylvania 

Fry,  Daniel  Joshua,  Jr  Studies  of  the  Origin  and  1  ests 

of  the  True  Oregon  Balsam. .. Oregon 

Gantert,  Charles  Louis  Mesquite  Gum   Pennsylvania 

Gehrung,  John  Clucas  An  Accounting  System  for  the 

Average-Sized  Drug  Store. ...  Ohio 

Gonya,  Harry  Herome  Calamine   Maine 

Gray,  John  Calvin  Gentian   Pennsylvania 

Greene,  Barnett  Russell   Hydrogen   Peroxide,  Production 

Past  and  Present  Pennsylvania 

Griffin,  William  Harold  Theatrical  Cold  Cream   New  York 

Hagenman,  Joseph  Jeremiah.  .Diluted  Acetic  Acid   Pennsylvania 


332  Philadelphia  College  of  Pharmacy.  {Am-JJu01y"'Jih4arm' 

Name  -  Thesis 

Hall,  Jasper  Bonsall  Liquor  Cresolis  Compositus  Maryland 

Harris,  George  Herbert  Paregoric  Pennsylvania 

Hayes,  John  Harry  Modern     Industrial  Reducing 

Agents   New  York 

Heckenberger,  William 

Welcome   The  Three  Cinnamons   Pennsylvania 

Held,  Ray  Charles   Accurate  Weighing   Pennsylvania 

Helwig,  George  L  Solution  of  Magnesium  Citrate. . Pennsylvania 

Hinman,  Ralph  Heber   Glycerophosphates   '....Pennsylvania 

Hurley,  William  James   Syrup  of  Quinine   Pennsylvania 

Johnson,  Clarence  Paul   Analysis  of  Viburnum  Opulus.  ..  Illinois 

Johnson,  Ernest  Irvin  Medication  of  Zinc  Stearate  Maryland 

Kahler,  Frank  Lot  Eucalyptus   Pennsylvania 

Kauffman,  Walter  Melvin  Structure  of  Viburnum  Opulus 

and  Various  Viburnum  Barks .  Pennsylvania 

Kentch,  Mortimer  Adrian  Medicated  Baths  and  their  Ex- 

)    temporaneous    Preparation  by 

the  Pharmacist   Pennsylvania 

Kinbach,  Edwin  Homer  [P.C]  Glass  Graduates   Pennsylvania 

Kostenbauder,  George  Henry. The  Extemporaneous  Preparation 

of  Medical  Bougies  Pennsylvania 

Krick,  Harry  Nunemacker.  . .  .Elixir  Terpini  Hydratis  ...... .".  .Pennsylvania 

Kulp,  Jacob  Harold  The  Evils  of  Newspaper  Prescrib- 
ing  Pennsylvania 

LaCourse,  Anthony,  Jr  Silicon  Carbide   New  York 

La  Wall,  Edgar  Seiple  Carbon  Dioxide  in  Atmospheric 

Air  and  Its  Estimation  Pennsylvania 

Leidich,  Stewart  Grier  tThe  Cultivation  and  Handling  of 

Golden  Seal   Pennsylvania 

Leinbach,  Allen  Abraham  Purity  of  Commercial  Gelatin. ..  Pennsylvania 

Llewellin,  Walter  Palmer  Bermuda  Arrowroot   Bermuda 

Lodge,  Roy  Paul  The  Electrolytic  Manufacture  of 

Organic  Compounds  and  Fine 

Chemicals   New  Jersey 

McCall,  Enzer  Lewis   Clay   Pennsylvania 

McKean,  Harold  Andrew  [P.C] The  Salt  Industry  in  New  York 

State   New  York 

McLarren,  Chester  Lee   Piscidia  Erythrina   Pennsylvania 

Marshall,  Forrest  Scott  Tea  and  Its  Caffeine  Yield  Pennsylvania 

Merz,  Elmer  Frank   The  Phosphates  of  Calcium  Pennsylvania 

Morehead,  Robert  Crosier.  ..  .Burgundy  Pitch   Virginia 

Murtoff,  Robert  Goulden  Acetylene   Pennsylvania 

Myers,  Nervin  Amos  Bacterins   Pennsylvania 

O'Hare,  Charles  Vincent  Oleum    Amygdalae    Amarse  et 

Benzaldehydum   Kentucky 

Owings,  Irl  Washington  Tablet  Making  in  the  Retail  Drug 

Store   Ohio 


Am'  j^°]yr*  i9i4arm' }    Philadelphia  College  of  Pharmacy.  333 

Name  Thesis 

Pettit,  Roland  Levi  Face  Creams  New  Jersey 

Rachmell,   Nathan  Cottonseed   Pennsylvania 

Rogers,  Ralph  Benjamin  Acacia   New  Jersey 

Rosenberg,  Julius  Jacob  Cork   New  York 

Rosoff,  Maurice  Drug    Standardization    and  Its 

Value  in  Pharmaceutical  Prep- 
arations  Pennsylvania 

Rowland,  Norris  Dean  Colorimetric  Test  for  Cubeb  Pennsylvania 

Russell,  Charles  Allen  Potassa  Sulphurata   Pennsylvania 

Salsbury,  Venola  Bruce  Emulsion  of  Cod  Liver  Oil  Pennsylvania 

Schadt,  Ralph  Monroe  Insecticides   Pennsylvania 

Semmel,  Irvin  Clarence  Prescription  Precipitation   Pennsylvania 

Shover,  Raymond  Leslie  Assay  of  Donovan's  Solution.  ...  Pennsylvania 

Shumaker,  Henry  Ward  Hygienic  Laboratory  of  the  U.  S. 

P.  H.  Service   Pennsylvania 

Slipakoff,  Isadore  Sponges   Pennsylvania 

Spangler,  Edwin  Royer  The  Rhizome  of  Asarum  Cana- 

dense  Pennsylvania 

Steever,  Ernest  Leo  Maple  Sap,  Syrup  and  Sugar  Pennsylvania 

Stines,  George  Findley  Carum   Ohio 

Sutton,  Stanley  Eugene  Colloids,    their    Chemistry  and 

their    Practical     and  Thera- 
peutical Applications   New  Jersey 

Taylor,  Leander  Gifford,  Jr.  ..Physiologic  Saline  Solution  New  Jersey 

Taylor,  William  Henry  Logwood   Pennsylvania 

Thompson,  Frank  Davenport.  . Peroxides  and  Perborates  Pennsylvania 

Train,  Earl  Fred  Manna   New  York 

Trambley,  Leo  Thomas  The  Chemistry  of  Paper  Making.  Pennsylvania 

Veigel,  Charles  Joseph   Volumetric  Estimation  of  Mer- 
cury  Pennsylvania 

Waker,  James  Schuteman  Aromatic   Fluidextract   of  Cas- 

cara   New  Jersey 

Watson,  John  Russell  Camphor:  Natural  and  Synthetic  Pennsylvania 

Watson,  Walter  Irving  Urinalysis   Rhode  Island 

Way,  John  Cloud,  Jr  The    Contributions    of  Ancient 

Greece  to  Modern  Medicine. .. Pennsylvania 

Weinstein.  Abram  Hirudo   Pennsylvania 

Wheeler,  Elwyn  J  Certified  Food  Colors   N.Hampshire 

Whipple,  Oscar  Kellog,  Jr.,. .  .Weeds  Used  in  Official  Pharmacy  New  Jersey 
White,  Charles  Albert,  Jr., 

[P-C]   Bee   Culture   and   Its  Products 

Used  in  Pharmacy  New  Jersey 

Willmers,  Horace  William  Sandalwood   Iowa 

Wolverton,  Fred  Cleveland ...  Podophyllum :  Fruit  and  Its  Ad- 
juvant Syrup  Ohio 

Wyman,  Abraham   Sodium  Chloride   Pennsylvania 


334  Philadelphia  College  of  Pharmacy.  {Amj^19u&rm- 

The  following  are  the  names  of  those  graduates  who  received 
the  degree  of  Pharmaceutical  Chemist  [P.C.],  together  with  the 
subjects  of  their  theses: 

Name  Thesis 
Flack,  George  Thomas   Unfermented  Grape  Juice,  Manu- 
facture and  Use  Pennsylvania 

Flottman,  Charles  August  Monazite  Sand   Pennsylvania 

Hansell,  Henry  Lewis  Compound  Syrup  of  Hypophos- 

phites   (Cloudy)   Pennsylvania 

Heinle,  Charles  Jacob  Paper   Pennsylvania 

Hogstad,  Anton,  Jr  Belladonna   Wisconsin 

Kutteroff,  Charles  Frederick.  .  Camphor  and  Its  Preparations  ...New  Jersey 
Porter,  Clarence  Frank  Turner  Methods  for  Recovering  Volatile 

and  Fixed  Oils  from  Emulsions  Tennessee 
Quin,  John  Frederick  Gartner. The    Production   of  Cottonseed 

Oil   Pennsylvania 

Schoonover,  Harold  Nelson. ..  Buttermilk  Cold  Cream   Pennsylvania 

Wallace,  William  Romine  The  Constituents  and  Manufac- 
ture of  Fertilizers   Pennsylvania 

Webb,  Alvin  Chester  Galke  ex  Rhus  glabra   New  Jersey 

Certificates  of  Proficiency  in  Chemistry  were  awarded  the 
following : 

Bush,  John  Lyol   Pennsylvania 

Cowles,  Henry  Carleton,  Jr  Pennsylvania 

Hinski,  Herman  Leo    [P.D.]   Pennsylvania 

Karns,  Harry  Clifford,  Jr.  [P.D.]   Pennsylvania 

Kind,  Paul  Adolph   New  Jersey 

Tucker,  George  W  Pennsylvania 

Certificate  of  Proficiency  in  the  Food  and  Drug  Course: 
Clark,  Roy  Lavender   Utah 

Certificates  in  Bacteriology  were  awarded  the  following: 

Aguizy,  Ahmed  Mahmoud  El   Egypt 

Atkins,  John  Walter  [P.D.]   Pennsylvania 

Brown,  West  Smith  [P.D.]  Pennsylvania 

Garrett,  Joseph  Jeffreys   Florida 

Hite,  Earle  Milton   Pennsylvania 

Huber,  Donald  Witherow   [P.D.]   Pennsylvania 

King,  James  David  [P.D.]   Pennsylvania 

Kulp,  Jacob  Harold   Pennsylvania 

Grauss,  Gustave  Adolph,  Jr  New  York 

Leathers,  Fred.  S  New  York 

Lemon,  Allan   Michigan 

Loehle,  Frank  Aloysius   New  York 


Am'ju!)y1r"i9i4arm'}    Philadelphia  College  of  Pharmacy.  335 

Linford,  Louis  George   New  York 

Merrier,  Paul  Marcus  Pfeiffer  Iowa 

Patterson,  Donald  Malcolm   New  Jersey 

Potterfield,  Garland  Blair   WestVirginia 

Sands,  Paul  Douglass  [P.D.]  Pennsylvania 

Shumaker,  Henry  Ward  Pennsylvania 

Smith,  John  Preston   Pennsylvania 

Spangler,  Edwin  Royer   Pennsylvania 

Starr,  Miss  Mabel  Connecticut 

Stein,  Joseph  Pennsylvania 

Wallace,  William  Romine  Pennsylvania 


Award  of  Prizes. 
The  Martin  Cup,  awarded  to  the  graduation  class  obtaining  a 
higher  average  than  the  one  immediately  preceding  it,  was  awarded 
to  the  class  of  1914  and  accepted  on  behalf  of  the  class  by  their 
president,  Elwyn  J.  Wheeler,  the  presentation  being  made  by  Presi- 
dent French. 

The  Welcome  Cup,  awarded  to  the  second  year  class  attaining 
a  higher  general  average  than  the  preceding  class  holding  it,  was 
awarded  to  the  class  of  191 5,  and  was  accepted  on  behalf  of  the 
second  year  class  by  their  president,  William  R.  Tenney,  the  presen- 
tation being  made  by  President  French. 

"  The  Graduate  191 3  "  Cup,  awarded  to  the  Freshman  class  for 
high  general  record  in  scholarship,  and  to  be  competed  for  by  suc- 
ceeding Freshman  classes,  was  for  the  first  time  presented  to  the 
Freshman  class  of  this  year  and  accepted  on  behalf  of  the  class 
by  their  president,  Harvey  V.  Stokely,  the  presentation  being  made 
by  Joseph  F.  Elward,  P.D.,  of  the  class  of  19 13. 

The  grade  of  distinguished  was  obtained  by  Stanley  E.  Sutton. 
The  following  attained  the  grade  of  meritorious:  W.  D.  Balliet, 
L.  Cohen,  E.  S.  La  Wall,  W.  R.  Wallace,  A.  C.  Webb,  A.  Weinstem. 

The  William  B.  Webb  Memorial  Prize,  a  gold  medal  and  certifi- 
cate, offered  for  the  highest  general  average  in  the  branches  of 
Committee,  Operative  Pharmacy  and  Specimens,  was  awarded  to 
Stanley  E.  Sutton,  the  presentation  being  made  by  Joseph  L. 
Lemberger. 

The  Chemistry  Prize,  $25,  offered  by  Prof.  Samuel  P.  Sadtler, 
for  knowledge  of  Quantitative  Chemical  Analysis,  was  awarded  to 
William  R.  Wallace.  Edgar  S.  La  Wall  received  honorable  men- 
tion in  connection  therewith. 

The  Materia  Medica  Prize,  $25,  offered  by  Prof.  Clement  B. 
Lowe,  for  the  best  examination  in  Materia  Medica  and  in  recog- 


336  Philadelphia  College  of  Pharmacy.  {AmjuJi0yUIi9uarni' 

nition  of  Materia  Medica  Specimens  with  a  meritorious  thesis,  was 
awarded  to  Anton  Hogstad,  Jr.  The  following  graduates  received 
honorable  mention  in  connection  therewith :  Woods  D.  Balliet, 
Edgar  S.  La  Wall,  Elmer  F.  Merz,  Nervin  A.  Myers,  Stanley  E. 
Sutton,  Alvin  C.  Webb  and  Elwyn  J.  Wheeler. 

The  Microscopic  Research  Prize,  a  compound  microscope,  of- 
fered by  Prof.  Henry  Kraemer,  for  the  most  meritorious  thesis 
involving  original  microscopic  work,  was  awarded  to  Anton  Hog- 
stad,  Jr.  The  following  graduates  received  honorable  mention  in 
connection  therewith :  Edmund  E.  Carr,  Daniel  J.  Fry,  Jr.,  William 
W.  Heckenberger,  Frank  L.  Kahler,  Walter  M.  KaufTman,  Norris  D. 
Rowland,  Edwin  R.  Spangler  and  Alvin  C.  Webb. 

The  Analytical  Chemistry  Prize,  $25,  offered  by  Prof.  Frank  X. 
Moerk,  for  the  best  work  in  qualitative  and  quantitative  analysis, 
was  awarded  to  William  R.  Wallace.  The  following  graduates 
received  honorable  mention  in  connection  therewith :  Stanley  E. 
Sutton  and  Alvin  C.  Webb. 

The  Operative  Pharmacy  Prize,  $20  in  gold,  offered  by  Prof. 
Joseph  P.  Remington,  for  the  best  examination  in  Operative  Phar- 
macy, was  awarded  to  Stanley  E.  Sutton.  The  following  graduates 
received  honorable  mention  in  connection  therewith :  Woods  D. 
Balliet,  Charles  F.  Kutteroff,  Forrest  S.  Marshall,  Edwin  R. 
Spangler,  Alvin  C.  Webb  and  Fred  C.  Wolverton. 

The  Maisch  Botany  Prize,  $20  in  gold,  offered  by  Mr.  Joseph 
Jacobs,  of  Atlanta,  Ga.,  was  awarded  to  Alvin  C.  Webb,  the  presen- 
tation being  made  by  Professor  Kraemer.  The  following  graduates 
received  honorable  mention  in  connection  therewith :  Edmund  E. 
Carr,  Daniel  J.  Fry,  Jr.,  Walter  M.  Kauffman  and  Edwin  R. 
Spangler. 

The  Mahlon  N.  Kline  Theoretical  Pharmacy  Prize,  a  Troemner 
Agate  Prescription  Balance,  for  the  best  examination  in  Theory  and 
Practice  of  Pharmacy,  was  awarded  to  Stanley  E.  Sutton,  the  pres- 
entation being  made  by  Joseph  W.  England. 

The  Commercial  Pharmacy  Prize,  $20  in  gold,  offered  by  Prof. 
Joseph  P.  Remington  to  the  graduate  who  passed  the  best  examina- 
tion in  Commercial  Training  at  the  final  examination  for  the  degree, 
was  awarded  to  John  C.  Gehrung,  the  presentation  being  made  by 
Prof.  E.  Fullerton  Cook.  The  following  graduates  received  hon- 
orable mention  in  connection  therewith :  Joseph  F.  Botdorf ,  Louis 
Cohen,  Meyer  C.  Epstein,  Nervin  A.  Myers,  Stanley.  E.  Sutton, 
Alvin  C.  Webb  and  Elwyn  J.  Wheeler. 


Ain.  Jour.  Pharin. 
July,  1914. 


Serial  Number  Abolished. 


337 


The  Instructors'  Prize,  $20,  offered  by  the  Instructors  of  the 
College,  for  the  highest  term  average  in  the  branches  of  Pharmacy, 
Chemistry  and  Materia  Medica,  was  awarded  to  Stanley  E.  Sutton, 
the  presentation  being  made  by  Prof.  F.  P.  Stroup.  The  following 
graduates  received  honorable  mention  in  connection  therewith : 
Charles  L.  Gantert,  Anthony  LaCourse,  Jr.,  Leo  T.  Trambley,  Alvin 
C.  Webb,  Abram  Weinstein  and  Elwyn  J.  Wheeler. 

The  Pharmacy  Quiz  Prize,  one  year's  membership  in  the  Ameri- 
can Pharmaceutical  Association,  offered  by  Prof.  Charles  H.  LaWall, 
for  the  best  term  work  in  Theory  and  Practice  of  Pharmacy,  was 
awarded  to  Alvin  C.  Webb.  The  following  graduates  received 
honorable  mention  in  connection  therewith :  Charles  L.  Gantert, 
Stanley  E.  Sutton,  Leo  T.  Trambley,  Abram  Weinstein  and  Elwyn 
J.  Wheeler. 

The  Special  Lecture  Report  Prize,  $10  in  gold,  awarded  for  the 
best  written  reports  of  the  series  of  special  lectures  held  under  the 
auspices  of  the  College,  session  1913-1914,  was  awarded  to  Charles  F. 
Kutteroff,  the  presentation  being  made  by  Dr.  A.  W.  Miller.  The 
following  graduates  received  honorable  mention  in  connection  there- 
with :  Louis  Cohen,  Charles  L.  Gantert,  Anton  Hogstad,  Jr.,  and 
Maurice  Rosoff. 

The  Kappa  Psi  Fraternity  Prize,  a  gold  medal,  offered  by  the 
Eta  Chapter  of  the  Kappa  Psi  Fraternity  to  the  graduate  making  the 
highest  general  average  during  the  senior  year  at  the  College,  was 
awarded  to  Stanley  E.  Sutton,  the  presentation  being  made  by  George 
L.  Holstein.  The  following  graduates  received  honorable  mention  in 
connection  therewith :  Edgar  S.  LaWall,  Alvin  C.  Webb  and 
Elwyn  J.  Wheeler. 


LEGEND  AND  SERIAL  NUMBER  ON  INSECTICIDES  AND 
FUNGICIDES  ABOLISHED. 

The  Three  Secretaries  Find  that  Guaranty  Legend  on  Substances  Used 
to  Destroy  or  Prevent  Insects  and  Fungi  is  Deceptive  and  Mis- 
leading. No  More  Serial  Numbers  to  be  Issued  or  Guaranties 
Accepted. 

Following  their  action  prohibiting  the  use  of  a  serial  number 
and  holding  the  guaranty  legend  on  foods  and  drugs,  under  the 
Food  and  Drugs  Act,  to  be  deceptive,  the  Secretaries  of  the 
Treasury,  Agriculture  and  Commerce,  on  June  30,  signed  an  amend- 


338 


Serial  Number  Abolished. 


Am.  Jour.  Pharm. 
July  1914. 


ment  to  the  regulations  under  the  Insecticide  Act  abolishing  the  use 
of  serial  numbers  on  insecticides  and  fungicides.  The  amended 
regulation  also  holds  that  the  use  of  the  legend  "  Guaranteed  by 
(name  of  guarantor)  under  the  Insecticide  Act  of  1910,"  on  the 
labelling  of  insecticides  and  fungicides,  or  similar  legends  is  mis- 
leading and  deceptive  in  that  the  public  is  induced  by  such  legend 
and  serial  number  to  believe  that  the  articles  to  which  they  relate 
have  been  examined  and  approved  by  the  Government. 

The  regulations,  therefore,  provide  that  the  use  of  the  guaranty 
legend  or  any  similar  legend  on  labels  or  packages  of  insecticides  or 
fungicides,  under  which  are  included  all  substances  for  destroying 
or  preventing  insects  or  fungi  affecting  plants  and  animals,  should  be 
discontinued. 

The  new  regulation  is  to  become  effective  on  and  after  May  1, 
1916.  In  the  case  of  products  packed  and  labelled  in  accordance 
with  the  Insecticide  Act  and  in  conformance  with  the  rules  and 
regulations,  prior  to  May  i,  191 6,  the  amendment  wiM  become  ef- 
fective on  and  after  November  1,  1916.  Manufacturers,  however, 
need  not  wait  until  May  1,  191 6,  to  change  their  labels,  but  are  free 
to  make  them  conform  to  the  new  regulations  at  any  time. 

As  in  the  case  of  the  ruling  on  foods  and  drugs,  the  amended 
regulation  as  to  insecticides  and  fungicides  provide  that  where  a 
wholesaler,  manufacturer  or  jobber  wishes  to  guarantee  his  goods 
so  as  to  protect  the  dealer  from  prosecution,  he  may  incorporate 
this  guaranty  in  or  attach  it  to  the  bill  of  sale,  invoice,  bill  of  lading, 
or  other  schedule.  As  the  protection  of  the  dealer  and  not  a  guaranty 
to  the  consumer  was  the  original  purpose  of  the  legend,  the  new 
method  fully  protects  the  dealer  without  misleading  the  consumer. 

In  the  meantime,  the  Department  notifies  the  public  that  the 
presence  of  a  serial  number  or  guaranty  legend  on  foods  and  drugs, 
or  on  insecticides  and  fungicides,  in  no  way  implies  that  the  Govern- 
ment has  tested  or  approved  such  articles,  or  guarantees  them  to  be 
in  compliance  with  the  Federal  law. 

Office  of  Information  .  , 

U.  S.  Dept.  of  Agriculture, 
Washington,  D.  C. 


THE  AMEKICAN 


JOURNAL  OF  PHARMACY 


A  CRITICISM  OF  THE  UNITED  STATER PH ARM ACpN^T A 
WITH  RESPECT  TO  THE  NAMlN5Q^FNTfi^K>M- 
POUND,  C17H21N04.HBr  +  3H20,  AND  WITH  REGARD 
TO  THE  PRESCRIBED  TESTS  FOR  ITS  IDENTITY  AND 
PURITY. 


Director  of  the  School  of  Pharmacy,  University  of  the  Philippines. 

On  the  Origin  and  Usage  of  the  Terms  Hyoscine  and 
Scopolamine. 

The  term  "  hyoscin  "  was  first  used  by  Reichardt  and  Hohn1  in 
1871  to  designate  a  basic  substance,  C8H15N02,  obtained  by  the  action 
of  barium  hydroxide  upon  hyoscyamine.  In  1880,  Ladenburg3  iso- 
lated an  alkaloid  from  the  mother-liquor  obtained  in  the  preparation 
of  the  so-called  amorphous  hyoscyamine  from  the  seeds  of  Hyoscya- 
mvis  niger.*  Ladenburg  found  the  composition  of  this  base  to  be  repre- 

1  Ann.  d.  Chem.  (1871),  157,  p.  107. 

2  Later,  the  composition  of  this  basic  substance  was  found  to  be  CSH13NO2 
and  became  known  under  various  names,  in  accordance  with  the  fancies  of 
the  respective  investigators — "  pseudotropin  "  (Ladenburg),  "  oxytropin  " 
(Ladenburg  and  Roth),  "  scopolin  "  (E.  Schmidt),  and  "  oscin  "  (Hesse). 

The  esters  of  the  base  CsHisNO;,  the  acetyl-,  benzoyl-,  and  cinnamyl- 
esters  were  manufactured  by  the  firm  of  E.  Merck  previous  to  the  year 
1898,  and  were  sold  under  the  name  of  "  Scopoleins,"  with  the  name  of  the 
acid  radical  as  a  prefix,  e.g.,  "  acetyl-scopolein." — Arch.  d.  Pharm.  (1898), 
236,  p.  33- 

3  Ber.  d.  deutsch.  chem.  Ges.  (1880),  13,  p.  1549. 

4  Bucheim  was  probably  the  first  investigator  to  isolate  the  so-called 
"  hyoscin."  He  obtained  two  basic  substances  from  the  seeds  of  Hyoscyamas 
niger,  one  of  which  he  describes  as  being  amorphous  and  oily,  the  other  as 
being  crystalline.  To  the  former  he  gave  the  name  "  hyoscyamin  "  and  to  the 
latter  the  name  "  sikeranin."  Cited  by  Ladenburg,  Ann.  d.  Chem.  (1881), 
206,  p.  283. 


AUGUST,  i9U 


By  A.  G.  DuMez, 


(339) 


340  Criticism  of  U.  S.  Pharmacopoeia,     {A\nJgZt'  imlm' 

sented  by  the  formula,  C17H23N03,  and  thought  it  to  be  isomeric 
with  hyoscyamine  and  atropine.  He  called  it  "  hyoscin,"  as  the 
compound  obtained  by  Reichardt  and  Hohn  was  then  thought  to  be 
identical  with  tropin,  a  decomposition  product  of  hyoscyamine.  In 
1888,  E.  Schmidt  and  Henschke5  obtained  an  alkaloid  from  the  root 
of  Scopolia  japonica,6  which,  from  the  analysis  and  properties  of  its 
aurichloride,  they  concluded  was  identical  with  the  "  hyoscin  "  of 
Ladenburg.  A  year  later,  Bender7-  isolated  hyoscyamine  and  what 
he  thought  was  a  new  crystalline  base  from  the  root  of  Scopolia 
atropoides.  A  quantity  of  this  crystalline  base  was  sent  to  E.  Schmidt 
for  analysis.  Bender  describes  the  properties  of  this  alkaloid  as 
found  by  Schmidt  under  the  name  "  scopclm.'1  The  analysis  of 
the  product  led  Schmidt  to  review  carefully  his  former  work  on  the 
base  obtained  from  Scopolia  japonica,  with  the  result  that  he  found 
the  composition  to  be  C17H21N048  instead  of  C17H23N03,  and  that 
it  was  identical  with  the  substance  received  from  Bender.  He  gave 
it  the  name  "  scopolamine'  Furthermore,  Schmidt  succeeded  in 
obtaining  this  base,  C17H21N04,  from  several  other  solanaceous 
plants  and  also  from  commercial  hyoscine  hydrobromide,  which 
was  then  being  prepared  by  the  firm  of  E.  Merck.  In  fact,  a  base 
having  the  formula  C17H23N03  and  corresponding  to  Ladenburg's 
"  hyoscin  "  could  never  again  be  isolated  from  the  mother-liquor 
resulting  in  the  crystallization  of  hyoscyamine,  its  absence  being 
conclusively  proven  by  L.  Merck9  in  1897. 

During  the  period  of  fifteen  years  following  the  work  of  Bender, 
the  literature  contains  a  considerable  number  of  publications  which 
tend  to  prove  or  disprove  the  identity  of  scopolamine  and  hyoscine, 

5  Arch.  d.  Pharm.  (1888),  226,  p.  185. 

6  Langaard,  in  1880,  reported  the  isolation  of  two  alkaloids  from  the 
root  of  Scopolia  japonica,  which  he  named  "  scopoleine "  and  "  rotoine " 
respectively. — Pharm.  Jonrn.  (1881),  n,  p.  10. 

Three  years  later,  Eykman,  working  with  the  same  root,  reported  the 
presence  of  but  one  alkaloid,  to  which  he  also  gave  the  name  "  scopolein." 
The  base  isolated  according  to  the  method  of  Eykman  was  being  prepared  and 
marketed  by  Merck  of  Darmstadt  and  Schuchardt  of  Gurlitz  as  early  as 
1888.  Upon  analysis,  Schmidt  found  the  product  to  be  a  mixture  of  "  hyoscin  " 
(Ladenburg),  hyoscyamine,  and  atropine. — Arch.  d.  Pharm.  (1888),  226,  p. 
187. 

7  Chcm.  Zeitung  (1890),  p.  805. 

8  Arch.  d.  Pharm.  (1892),  220,  p.  207. 

8  Journ.  Soc.  Chcm.  Industr.  (1897),  T6,  p.  515. 


Am\n»Ts[;  iP9i4rm'}     Criticism  of  U.  S.  Pharmacopoeia,  341 

some  of  which  also  tend  to  show  the  desirability  of  establishing  the 
usage  of  the  term  scopolamine  in  preference  to  hyoscine,  or  vice 
versa.  The  controversy  was  carried  on  principally  by  O.  Hesse  and 
E.  Schmidt,  with  an  occasional  opinion  from  others. 

In  1892,  when  Hesse10  published  his  results  on  the  identification 
of  the  Solanaceous  alkaloids,  he  agreed  with  Schmidt  that  the  com- 
position of  "hyoscin"  (Ladenburg)  should  be  represented  by  the 
formula  C17H21N04  and  that  it  was  identical  with  "  scopolamin," 
but  objected  to  the  introduction  of  the  latter  term,  as  the  hydro- 
bromide  had  already  been  marketed  for  ten  years  under  the  name  of 
"  hyoscinhydrobromid."  Later,  however,  Hesse  concluded  that  the 
two  were  not  identical,  as  4k  hyoscin  "  was  known  to  be  lsevo rotatory, 
and  he  succeeded  in  isolating  a  quantity  of  an  optically  inactive  base 
from  commercial  scopolamine  hydrobromide.  This  led  him  to  be- 
lieve that  "  scopolamin  "  was  a  mixture  of  "  hyoscin  "  and  the  new 
base  to  which  he  gave  the  name  "  atroscin."11  As  early  as  1890, 
Schmidt12  observed  that  the  hydrobromide  was  laevorotatory.  He 
also  discovered  that  solutions  of  the  active  scopolamine  hydro- 
bromide could  be  rendered  optically  inactive  by  the  addition  of 
small  quantities  of  sodium  or  potassium  hydroxide.  This  change 
he  attributed  to  the  conversion  of  the  optically  active  base  into  an 
inactive  isomer,13  which  he  later  isolated  and  called  "  inactive  scopo- 
lamin." The  identity  of  "  atroscin  "  (Hesse)  with  the  latter  was 
conclusively  proven  by  the  work  of  Gadamer14  and  Kuntz-Krause15 
respectively. 

The  alkaloid  represented  by  the  formula,  C17H21N04,  was  first 
placed  upon  the  market  in  the  form  of  the  hydrobromide  by  Merck 
of  Darmstadt.  It  was  then  being  prepared  from  the  base  isolated 
from  the  seeds  of  Hyoscyamus  niger  and  was  sold  under  the  name 
of  "  hyoscinhydrobromide."  About  1894,  shortly  after  the  work  of 
Bender  and  Schmidt,  scopolia  root  became  recognized  as  a  source 
of  supply.  However,  the  hydrobromide,  when  prepared  from  the 
base  obtained  from  the  latter  source,  was  marketed  as  "  skopolamin- 

10  Ann.  d.  Chcm.  (1892),  271,  p.  111. 

11  Bcr.  d.  deutsch.  chcm.  Ges.  (1896),  29,  p.  1781.  The  term  "atroscin" 
has  never  received  recognition  by  other  investigators. 

12  Arch  d.  Pharm.  (1892),  230,  p.  207. 

13  Ibid.  (1894),  232,  p.  409- 
"Ibid.  (1898),  236,  p.  382. 

ir'Journ.  f.  prakt.  Chcm.  (1910),  64,  p.  569. 


342  Criticism  of  U.  S.  Pharmacopoeia.     \kmi*™*{  Si™1 

hydrobromid."  Thus,  E.  Merck,10  in  1896,  remarked  that  the  alka- 
loids, hyoscine  and  scopolamine,  were  identical,  but  that  the  name 
hyoscine  was  given  to  the  base  when  isolated  from  Hyoscyamus 
niger,  while  the  term  scopolamine  was  applied  to  that  isolated  from 
scopolia  root. 

In  1897,  L.  Merck17  called  attention  to  some  observations  in- 
dicating that  the  hydrobromide  prepared  from  the  alkaloid  obtained 
from  Hyoscyamus  niger  was  fairly  constant,  showing  a  specific 
rotatory  power  of  — 240  to  — 250  ;  while  that  prepared  in  a 
like  manner  from  the  alkaloid  when  obtained  from  scopolia  root 
varied  and  showed  a  much  lower  specific  rotatory  power,  —  I3.47°.1S 
From  the  foregoing  observations  one  would  naturally  infer  that 
the  designation  hyoscine  hydrobromide  would  insure  a  product 
strongly  lsevorotatory  and  containing  little  of  the  optically  inactive 
isomer,  while  the  term  scopolamine  hydrobromide  would  indicate  a 
salt  having  a  low  specific  rotatory  power.  Such,  however,  is  not  the 
case,  exactly  the  reverse  being  true  at  the  present  time.  The  observa- 
tions of  Schmidt,19  Hesse,-0  Luboldt,21  and  others  show  that  the 
commercial  salt,  the  hydrobromide,  regardless  of  its  natural  source, 
often  varied  in  its  rotatory  power.  Schmidt  attributed  this  variation, 
in  the  case  of  the  salt  prepared  from  Hyoscyamus  niger,  to  the  use  of 
strong  alkalies,  such  as  the  hydroxides  of  sodium  and  potassium,  or 
even  their  normal  carbonates  on  long  standing,  in  the  isolation  of 
the  free  base.  Furthermore,  it  was  found  that  the  name  given  to 
the  commercial  product  was  no  indication  of  this  variation,  the  salt 
designated  hyoscine  hydrobromide  varying  as  well  as  that  bearing 
the  name  scopolamine  hydrobromide.  However,  upon  the  introduc- 
tion into  the  German  Pharmacopoeia  22  of  the  term  "  Skopolamin- 

la  Merck's  Bericht  (1894),  p.  94. 

"  Journ.  Soc.  Chem.  Industr.  (1897),  16,  p.  515. 

ls  Schmidt  noted  a  specific  rotatory  power  of  -250  43'  for  scopolamine 
hydrobromide  prepared  from  the  base  obtained  from  the  root  of  Scopolia 
atropoides.  He  is  of  the  opinion  that  the  low  rotatory  power  observed  by 
Merck  was  due  to  the  presence  of  i-scopolamine  which  may  preexist  in  the 
plant  at  certain  seasons  of  the  year  or  which  may  be  formed  in  the  process 
of  curing. — Arch.  d.  Pharm.  (1898),  236,  p.  59. 

wApoth.  Ztg.  (1896),  11,  p.  260. 

20  Ibid.  (1895),  10,  p.  187. 

21  Arch.  d.  Pharm.  (1898),  236,  pp.  11-47. 

22  Deutsches  Arzneibuch,  5th  Edit.,  Berlin  (1910),  p.  451. 


AmAuguUst*  iP9Hrm'}     Criticism  of  U.  S.  Pharmacopoeia,  343 

hydrobromid  "  with  the  specific  rotatory  power  as  a  test  for  its 
identity  and  purity,  German  manufacturers  began  producing  the 
lsevo-salt  to  the  exclusion  of  that  having  little  or  no  rotatory  power. 
Hence  the  name  scopolamine  hydrobromide,  in  Germany  at  least,  now 
signifies  the  lsevo-compound. 

That  the  present  tendency  in  England  is  to  apply  the  name 
scopolamine  hydrobromide  in  a  manner  similar  to  that  of  the  Ger- 
man Pharmacopoeia,  while  hyoscine  hydrobromide  is  being  used 
to  designate  the  salt  having  the  weaker  rotatory  power,  is  evidenced 
in  the  following: 

(a)  Spencer  Sheill23  states  that  scopolamine  is  used  by  some  to 
represent  the  laevo-compound,  while  hyoscine  is  applied  by  others  to 
the  mixture  of  the  lsevo-  and  inactive  varieties  having  the  weaker 
rotatory  power. 

(b)  A  statement  similar  to  the  latter  is  also  given  in  the  Extra 
Pharmacopoeia  of  Martindale  and  Westcott.24 

(c)  Finnemore  and  Braithwaite25  report  that  English  physicians 
use  the  term  scopolamine  hydrobromide  when  prescribing  rather 
than  hyoscine  hydrobromide  in  order  to  be  sure  of  securing  the 
German  preparation,  which  is  lsevorotatory. 

From  the  survey  of  the  literature,  it  appears  that  the  designation 
hyoscine  hydrobromide  is  still  given  preference  in  the  United  States, 
although  practically  all  of  the  salt  is  imported  from  Germany  and  is 
now  being  received  largely  as  the  lsevo-variety. 

A  more  concrete  idea  of  the  variations  in  the  naming  of  the  alka- 
loid and  its  salt,  the  hydrobromide,  may  be  obtained  from  the 
following  tabulations : 

TABLE  NO.  1. 

Names  Applied  to  the  Free  Base  or  Related  Compounds. 


Atroscin. 


Hyoscin . 


Hesse,  1896  =  Ci7H2iN04,  isolated  from  commercial  scopolamine 
hydrobromide,  optically  inactive  and  identical  with 
i-scopolamine. 

Reichardt  and  Hohn,  1871  =CsHi5NO,  a  decomposition  product  of 
hyoscy  amine. 

Ladenburg,  1880  =  CnH23N03,  isolated  from  Hyoscyamus  niger. 
Schmidt  and  Henschke,  1 888  =  a  base  isolated  from  Scopolia  japonica. 
Hesse,  1892  =  C17H21NO4,  isolated  from  Hyoscyamus  niger. 
E.  Merck,  1894  =  Ci7H2iN04,  isolated  from  Hyoscyamus  niger. 


23  Lancet  (1910),  11,  p.  29. 

24  Martindale  and  Westcott,  Extra  Pharmacopoeia,  London  (1912),  p.  444. 

25  Year-Book  of  Pharm.  and  Trans.  (1912),  p.  498. 


344 


Criticism  of  U.  S.  Pharmacopoeia. 


( Am.  Jour.  Pharm. 
(      August,  1914. 


Scopolamin. 


Inactive 
Scopolamin. 

Scopoleine. . 

Scopoleins. . 
Scopolin. . . . 


Schmidt,  1890  =  Ci7H2iN04,  isolated  from  Scopolia  japonica. 
Schiitte,  1 89 1  =Ci7H2iN04,  isolated  from  Datura  stramonium. 
Schmidt,  1892  =  Ci7H2iN04,  isolated  from  Datura  stramonium,  Du- 

boisia  myoporoides,  and  Atropa  belladonna. 
E.  Merck,  1894  =  d7H21N04,  isolated  from  Scopolia  root. 
Thorns  and  Wentzel,  1898  =  C17H21NCX1,  isolated  from  Mandragora 

root. 

Schmidt,  1896  =  Ci7H2iN04,  the  optically  inactive  isomer. 

fLangaard,  1881  =a  mixture  of  alkaloids  from  Scopolia  japonica, 

\  principally  C]7H2iN04. 

<!  Firm  of  Merck,  1898  = esters  of  the  base,  C8Hi:jN02. 

-{Bender,  1890  =  CnH2iN04,  isolated  from  Scopolia  japonica. 

TABLE  NO.  2. 


Official  Names  and  Synonyms  of  the  Hydrobromide. 


British  Pharmacopoeia,  1898. 


Hyoscinae  hydrobromicum  

Hyoscine  hydrobromide  

Hydrobromate  of  hyoscine  

Scopolamine  hydrobromide  

Hyoscinae  hydrobromidum  

Hyoscine  hydrobromide  

Hyoscinae  hydrobromas,  1890  ^United  States  Pharmacopoeia,  1905. 

Scopolaminae  hydrobromidum  | 

Scopolamine  hydrobromide  J 

Neither  the  free  base  nor  its  salt,  the  hydro- \™       ,  ^  0 

bromide,  is  official  :   ...  .  j  French  Pharmacopoeia,  1908. 

Bromidato  di  Scopolamina  ^Italian  Pharmacopoeia,  1909. 

IS^^dS^micum:::::: : : :  :}G—  p— op^a,  t9I0. 

On  the  Physiological  Action  of  Scopolamine. 

Scopolamine  is  an  ester  of  tropic  acid  and  the  base,  scopolin,20 
and,  like  the  closely  related  hyoscyamine,  may  exist  in  three  stereo- 
isomeric  forms.  Two  of  these,  the  kevo-  and  racemic  forms,  are 
known.  These  isomers,  like  those  of  nicotine27  and  hyoscyamine,28 
differ  in  their  physiological  action  as  well  as  in  their  chemical  and 
physical  properties. 

The  early  investigators  who  attempted  to  discover  a  difference  in 
the  physiological  action  of  the  two  isomers  did  not  work  with  the 
material  prepared  in  their  own  laboratories,  and  very  probably 
used  the  salts  in  an  impure  state ;  i.e.,  as  mixtures  of  the  two  isomers 
or  with  small  amounts  of  other  impurities29  present.    Add  to  this 

2t;  Gadamer,  Arch.  d.  Pharm.  (1901),  239,  p.  321. 

27  Ber.  d.  deutsch.  chem.  Ges.  (1904),  37,  p.  1234. 

28  Cushny,  Journ.  of  Physiol.  (1904),  30,  p.  176. 

29  Schmidt,  Scopolamine  hydrobromide  with  a  low  specific  rotatory  power 
contains  a  small  amount  of  an  impurity  not  easily  detected. — Arch.  d.  Pharm. 
(1905),  243,  p.  4. 


AmAuguUst'  i9hiim'}     Criticism  of  U.  S.  Pharmacopoeia,  345 

the  lack  of  chemical  knowledge  concerning  the  substance  with 
which  they  were  working  and  we  can  readily  understand  why  they 
obtained  varying  and  sometimes  contradictory  results. 

Konigshoefer30  reported  that  the  effect  of  atroscine  (i-scopo- 
lamine) upon  the  accommodation  takes  place  with  greater  rapidity 
and  is  of  longer  duration  than  in  the  case  of  scopolamine  (1- 
scopolamine).  Under  pathological  conditions  (iritis)  he  also  found 
its  action  to  be  the  more  energetic. 

Meyer  confirmed31  the  latter  finding,  but  stated  that  he  could  not 
agree  with  Konigshoefer  with  respect  to  the  action  on  the  accommoda- 
tion. 

Uhthoff  and  Axenfeld32  could  find  no  difference  in  the  physiologi- 
cal action  of  scopolamine  hydrobromide  having  a  specific  rotatory 
power  of  — 25. 430  and  that  having  specific  rotatory  power  of 
—  6.620. 

In  more  recent  years  the  work  has  been  taken  up  with  a  greater 
knowledge  of  the  chemistry  of  the  isomers  and  under  more  ad- 
vantageous conditions,  with  the  result  that  real  differences  in  their 
physiological  activity  have  been  found  and  clearly  described. 

Cushny  and  Peebles33  found : 

(a)  That  the  action  of  1-scopolamine  on  the  terminations  of  the 
secretory  nerves  in  the  salivary  glands  and  on  the  terminations  of 
the  inhibitory  fibres  of  the  heart  was  double  that  of  i-scopolamine 
in  effect;  from  which  they  inferred  that  a  similar  ratio  might  hold 
in  other  analogous  terminations. 

(b)  That  1-  and  i-scopolamine  produce  the  same  effect  in  a  like 
degree  upon  the  central  nervous  system  in  man  and  mammals  and 
on  the  terminations  of  the  motor  nerves  in  the  frog. 

E.  Hug,34  from  a  series  of  experiments  On  dogs  and  cats,  con- 
cluded : 

(a)  That  the  action  of  1-scopolamine  on  the  vagus  is  three  to 
four  times  as  great  in  strength  as  that  of  i-scopolamine. 

(b)  That  1-scopolamine  acts  twice  as  energetically  as  i-scopo- 
lamine upon  the  oculomotorius. 

Evidence  to  the  effect  that  a  difference  in  the  physiological  action 

30  Cited  by  Hesse,  Ber.  d.  deubsch.  chem.  Gcs.  (1896),  27,  p.  1781. 

31  Cited  by  E.  Schmidt,  Arch.  d.  Phar,  (1897),  236,  p.  71. 

32  Cited  by  L.  Merck,  Pharm.  Journ.  (1897),  71,  p.  41, 

33  Joum.  of  Physiol.  (1905),  32,  pp.  501-510. 

34  Arch.  f.  exp.  Path.  u.  Pharmak.  (1912),  69,  p.  56. 


346 


Criticism  of  U.  S.  Pharmacopoeia, 


Am.  Jour.  Pharm. 
August,  1914. 


of  the  commercial  preparations  has  been  observed  by  medical  practi- 
tioners is  amply  supplied  in  the  literature.  In  fact,  the  references 
are  too  numerous  to  be  included  in  this  paper.  However,  the  state- 
ment of  Finnemore  and  Braithwaite35  in  connection  with  the  use  of 
hyoscine  and  scopolamine  hydrobromides  by  English  physicians  is 
quoted  because  of  the  direct  application : 

"  Anaesthetists  have  expressed  a  preference  for  the  German 
preparations  sold  under  the  name  of  '  Scopolamine  hydrobromide ' 
owing  to  the  variable  results  obtained  following  the  administration 
of  the  product  known  as  '  Hyoscine  hydrobromide.' 

On  the  Tests  eor  Identity  and  Purity. 

The  chemical  and  physical  properties  of  scopolamine  and  its 
salts  have  been  quite  thoroughly  worked  up  by  E.  Schmidt,  O.  Hesse, 
Gadamer,  and  others.  There  is,  however,  some  uncertainty  con- 
cerning the  melting-points  of  the  chloraurates  of  both  the  1-  and  i- 
scopolamine,  the  greater  number  of  the  investigators  confirming  the 
results  obtained  by  Schmidt.  The  following  tables  show  the  im- 
portant physical  constants  of  the  hydrobromides  as  obtained  by 
various  investigators  and  as  given  in  the  United  States,  British,  and 
German  Pharmacopoeias : 

TABLE  NO.  3. 


Name  of 
investigator. 

Stero- 
isomer. 

M.  P.  of 

the  anhy- 
drous salt. 

M.  P.  of 

the  chlo- 
raurate. 

M.  P.  of 

the  hydro- 
brom-chlo- 
raurate. 

M.  P.  of 
the  picrate. 

Specific  ro- 
tatory 
power  in 
aqueous 
solution. 

E.  Schmidt*  

Laevo- 
Inactive 
Inactive 
Lsevo- 

193-194° 
i8o° 

212-2140 
208-2100 

208° 

208-2090 
205° 

198° 

201-202° 

187-188° 

-25°  43' 

0° 
0° 

-25°52' 

E.  Schmidt  

Kircher38  

Thorns  and  Wentzel39. 
0.  Hesse40  



Laevo- 

Inactive 
Laevo- 

192-1970 
1810 

-25. 7°  to 
-25-9° 

0° 

0.  Hesse  

Jowett41  

About  215 

35  Year-Book  of  Pharm.  and  Trans.  (1912),  p.  498. 

36  Arch.  d.  Pharm.  (1898),  236,  p.  59. 

37  Ann.  d.  Chem.  (1900),  310,  p.  352. 

38  Arch.  d.  Phar.  (1905),  243,  p.  321. 

39  Ber.  d.  deutsch.  chem.  Gcs.  (1898),  31,  p.  2037. 

40  Journ.  f.  prakt.  Chem,  (1901),  64,  2,  p.  364. 
^Journ.  Chem.  Soc.  (1897),  71,  p.  678. 


Am.  Jour.  Pharm. 
August,  1914. 


Criticism  of  U.  S.  Pharmacopoeia, 


347 


In  explanation  of  the  table  it  should  be  stated  that  Schmidt  and 
Gadamer  determined  the  melting-points  of  the  various  salts,  using  a 
capillary  tube  and  sulphuric  acid  bath ;  Hesse  used  a  "  Roth's  " 
apparatus.  Schmidt  found  the  melting-point  of  the  chloraurate  of 
the  1-  salt  to  be  208 °  to  209 0  when  determined  with  the  "  Roth's  " 
apparatus.42 

TABLE  NO.  4- 


Pharmacopoeia. 

Per  cent,  of  H2O  lost  in  dry- 
ing at  ioo°  C.  or  over  H2SO4 

M.  P.  of  the 
anhydrous  salt. 

M.  P.  of  the 
chloraurate. 

Specific  rota- 
tory power  of 
a  5  per  cent, 
aqueous  solu- 
tion at  15°  C 

United  States43.  . 
British44  

179-7° 
1 93- 1 94° 
About  1900 

197° 
198° 

More  than  12  per  cent. 
12.3  per  cent. 

German45  

-24°  45' 

A  comparison  of  the  constants  as  given  in  Tables  No.  3  and  No.  4 
shows  the  melting-point  (179.70  C.)  of  the  anhydrous  hydrobromide 
as  specified  in  the  United  States  Pharmacopoeia  to  agree  very  closely 
with  that  (1800  C.)  found  by  Schmidt  or  Hesse  (1810  C.)  for  i- 
scopolamine  hydrobromide;  while  the  melting-point  (1970  C.)  of 
the  chloraurate  as  given  in  the  pharmacopoeia  corresponds  very  well 
with  that  (1980  C.)  found  by  Hesse  for  the  chloraurate  of  1-scopo- 
lamine.  According  to  two  observers,  the  melting-point  of  the  hydro- 
bromide alone  is  no  indication  as  to  the  respective  quantities  of  the 
1-  and  i-isomers  present  in  the  commercial  salt ;  e.g.,  Schmidt46  found 
a  melting-point  of  i8o°-i8i°  C.  for  the  commercial  hydrobromide, 
[a]D  =  —  130  30';  Hesse47  obtained  a  melting-point  of  1780  C.  for 
a  sample  of  the  hydrobromide,  [a]D  =  —  21. 30.  If  we  take  into 
consideration  the  fact  that  the  hydrobromides  of  both  the  lsevo-  and 
the  inactive  forms  crystallize  with  3H0O,  and  that  the  melting-points 
of  the  chloraurates  have  not  yet  been  definitely  established,  it  be- 
comes evident  that  the  pharmasppoeial  tests  for  the  identity  of  this 
compound  are  worthless. 

That  physical  constant  which  has  been  found  to  give  the  most 
accurate  indication  as  to  the  purity  of  1-scopolamine  or  its  salts, 


42  Arch.  d.  Phar.  (1894),  232,  p.  417. 

43  U.  S.  P.,  8th  Rev.  (1905),  P-  39L 
"British  P.  (1898),  p.  153. 

45  Deutsches  Arzneibuch,  5th  Edit.,  Berlin  (1910),  p.  451. 

48  Arch.  d.  Pharm.  (1898),  236,  p.  62. 

47  Jour n.  f.  prakt.  Chan.  (1901),  64,  2,  p.  385. 


348  Criticism  of  U.  S.  Pharmacopoeia.     -j  An^u^J-  ^rm' 

both  with  respect  to  the  presence  of  the  inactive  variety  and  to 
foreign  substances,  is  the  specific  rotatory  power.  This  has  been 
found  to  be  between  — 240  and  — 25 0  for  the  fairly  pure 
anhydrous  hydrobromide  in  a  5  per  cent,  aqueous  solution  at  150  C. 
A  specific  rotatory  power  of  — 32. 30  to  — 32.90  has  been  found 
by  Hesse48  for  the  salt  in  a  high  state  of  purity.  Determinations 
of  this  constant  have  revealed  the  following  variations  in  the 
commercial  product: 

1894 —  E.  Schmidt49:  Scopolamine  hydrobromide  from  Gehe  and  Com- 
pany, Dresden,  [a]  D  =  —  14.58  °. 

1895 —  E.  Schmidt50:  Scopolamine  hydrobromide  from  E.  Merck,  Darm- 
stadt,   [a]  D  =  —  17  0  9'. 

1895 —  Gadamer  51 :  Scopolamine  hydrobromide  from  Gehe  and  Company, 
Dresden.  Anhydrous  salt  in  aqueous  solution,  p  =  6.3043,  t  =  19.80  C, 
[a]  D  =  — 6.62°. 

1896 —  O.  Hesse52:  Five  commercial  samples  of  scopolamine  hydrobromide 
showed  a  specific  rotatory  power  as  follows:  — 22.1  °,  — 12.7  °,  — 12. 1  °, 
—  11.3  °,  —  10.0  °. 

1897 —  L.  Merck53:  Scopolamine  hydrobromide  from  Scopolia  root, 
[a]  D  = —  13-47°.  Scopolamine  hydrobromide  from  the  seed  of  Hyoscyamus 
niger,  [a]  D  = —  240  to  —  250. 

1898 —  Luboldt54:  Scopolamine  hydrobromide  from  Gehe  and  Company, 
Dresden.  1.5304  Gm.  of  anhydrous  salt  in  aqueous  solution,  d  =  1.0096, 
t  =  i5°,  [a]  D  =  i4°  58'. 

1899 —  O.  Hesse  55 :  Scopolamine  hydrobromide,  commercial.  Anhydrous 
salt  in  aqueous  solution,  p  =  4,  t  =  150,  [a]  D=  —  7.50. 

1901 — Gadamer56:  Scopolamine  hydromide  from  E.  Merck,  Darmstadt. 
[a]  D  =  —  24.69°. 

1912 — E.  Hug57:  Scopolamine  hydrobromide  from  Hoffmann-La  Roche 
Company,  Grenzach.  Anhydrous  salt  in  aqueous  solution,  p  =  4.5,  [a]  D 
=  —  26.0°. 

1912 — Finnemore  and  Braithwaite 58 :  Four  samples  of  commercial  hyoscine 
hydrobromide  showed  a  specific  rotatory  power  as  follows:  —23°  7',  —  21  0 
59',  —  21°  25',  —  6°  30';  one  sample  was  found  to  be  inactive. 

isJoum.  f.  prakt.  Chem.  (1901),  64,  2,  p.  385. 
4»Apoth.  Ztg.  (1896),  11,  p.  260. 
60  Ibid. 

51  Cited  by  Schmidt,  Arch.  d.  Pharm.  (1898),  236,  p.  47. 
52Ber.  d.  dentsch.  chem.  Gcs.  (1896),  29,  p.  1780. 
63 lourn.  Soc.  Chem.  Industr.  (1897),  16,  p.  575. 

54  Arch.  d.  Phar.  (1898),  236,  p.  14. 

55  Ann.  d.  Chem.  (1899),  309,  p.  90. 

56  Arch.  d.  Phar.  (1901),  239,  p.  324. 

"Arch.  f.  exp.  Path.  u.  Pharmak.  (1912),  69,  p.  48. 
58  Phar.  lourn.  and  Trans.  (1912),  p.  498. 


AlAugust'  1914™'}  Constituents  of  Androgr aphis  Paniculata.  349 

Conclusions  and  Suggestions. 

1.  Practically  all  of  the  scopolamine  hydrobromide  or  the  so- 
called  hyoscine  hydrobromide  consumed  in  the  United  States  is  at 
present  supplied  by  Germany,  where  the  laevo-compound  only  is 
recognized  as  official  under  the  title  "  Skopolaminhydrobromid."  In 
view  of  this  fact,  and  as  present  usage,  not  only  in  Germany  but  in 
other  continental  countries  and  in  England,  indicates  a  preference 
for  the  latter  term,  there  can  be  no  important  reason  for  the  same 
compound  appearing  under  two  different  titles  in  the  United  States 
Pharmacopoeia.  It  is  therefore  suggested  that  the  term  "  Scopo- 
lamine hydrobromide  "  be  made  the  official  English  title  in  the  next 
revised  edition  of  the  pharmacopoeia,  with  "  Hyoscine  hydrobro- 
mide "  as  a  possible  synonym. 

2.  As  there  is  still  some  doubt  concerning  the  exact  melting- 
point  of  the  chloraurate  of  either  the  1-  or  i-scopolamine,  this  con- 
stant should  not  be  prescribed  as  a  test  by  the  next  pharmacopoeia. 

3.  It  is  now  known  that  scopolamine  or  the  so-called  hyoscine 
may  exist  in  either  the  laevo-  or  inactive  forms,  and  that  the  com- 
mercial hydrobromide  is  usually  the  lsevo-salt,  but  not  infrequently 
a  mixture  of  the  two  isomeric  forms.  It  is  also  known  that  the 
isomers  produce  different  physiological  effects,  the  laevo-  variety  pre- 
ferred by  medical  practitioners  because  of  its  particular  physiological 
action  and  on  account  of  its  constant  state  of  purity.  It  is  therefore 
suggested  that  the  revised  edition  of  the  United  States  Pharma- 
copoeia recognize  only  the  1-scopolamine  hydrobromide  as  official, 
and  that  a  definite  specific  rotatory  power  be  prescribed  for  it. 


CONSTITUENTS  OF  ANDROGR  A  PHIS  PANICULATA. 

By  KSHITIBHUSHAN  BHADURI,  M.Sc. 

Androgr  aphis  paniculata,  Nees  (Fam.  Acanthacecc) ,  is  a  common 
bitter  plant  growing  throughout  the  plains  of  India.  The  plant  is  an 
annual  one,  two  to  three  feet  long;  stem  quadrangular,  pointed, 
smooth;  leaves  opposite,  on  short  petioles,  lanceolate,  entire  upper 
surface  dark  green  and  shining,  under  surface  paler  and  finely 
granular;  they  vary  much  in  size,  but  the  larger  are  usually  three 
inches  in  length  and  one  inch  in  breadth ;  calyx  deeply  five-cleft, 
corolla  bilabiate,  tips  linear,  reflected,  upper  one  three-toothed,  lower 


350 


Constituents  of  Andrographis  Paniculata. 


Am.  Jour.  Pharm. 
August,  1914. 


one  two-toothed;  flowers  remote,  alternate,  long  petioles,  downy, 
rose  colored  or  white  streaked  with  purple;  capsules  erect,  some- 
what cylindrical ;  seeds,  three  to  four  in  each ;  roots  fusiform,  simple 
woody  with  numerous  fine  radicles. 

The  plant  is  well  known  in  Bengal  under  the  name  of  Kalmegh, 
and  is  the  principal  constituent  of  a  domestic  medicine  named  Alui 
which  is  given  to  children  for  the  relief  of  griping,  irregularity  of 
bowels,  and  loss  of  appetite.  It  is  also  called  Kiryat,  and  is  used  as 
a  substitute  for  chirata.  It  is  called  in  Sanskrit  "  Mahatikta,"  or 
king  of  bitters. 

According  to  Dr.  W.  A.  Boorsma  (Mededeelingen  uit  S  Lands 
plantentium,  1896,  xviii,  63),  if  the  powdered  plant  be  mixed  with 
lime  and  submitted  to  steam  distillation,  the  distillate  gives  all  the 
tests  of  a  volatile  alkaloid  which  he  could  not  isolate.  He,  however, 
isolated  an  amorphous  bitter  substance  (C15H2704). 

He  says  that  the  substance  begins  to  decompose  before  melting, 
so  that  he  could  not  determine  its  melting-point  accurately.  The 
amorphous  substance  obtained  by  the  present  author  has  some 
properties  common  with  the  above  substance,  but  the  melting-point 
has  been  accurately  determined ;  while  the  above  author  says  that 
the  amorphous  and  crystalline  (also  obtained  by  him)  substances 
have  the  same  properties,  the  two  substances  described  herein  have 
very  different  properties. 

Dr.  K.  Gorter,  by  extracting  the  leaves  of  Andrographis  panicu- 
lata with  alcohol,  obtained  a  lactone  (C22H30O5)  named  andrographo- 
lite.  It  is  converted  into  salts  of  andrographic  acid  by  boiling  with 
caustic  alkalies  (Apoth.  Zeits.,  191 1,  26,  954). 


For  examination  68  Gm.  of  the  powdered  leaves  and  stems  were 
taken  and  exhausted  in  a  Soxhlet  apparatus  successively  by 
petroleum  ether,  ether,  chloroform,  and  alcohol ;  after  evaporation 
of  the  solvents  the  extracts  weighed: 


Experimental. 


Petroleum  ether 

Ether   

Chloroform  .  .  . 
Alcohol   


0.437  Gm.,  or  0.643  per  cent. 
0.5864  Gm.,  or  0.861  per  cent. 
2.2501  Gm.,  or  3.309  percent. 
1.5045  Gm.,  or  2.214  percent. 


Total 


7.027  per  cent. 


Aba4S"  num'}  Constituents,  of  Andrographis  Paniculata.  351 

55  Gm.  of  substance  on  burning  gave  9.7802  Gm.  or  17.782  per 
cent,  of  ash. 

The  plant  is  very  rich  in  chlorophyll,  one  portion  of  which  is 
soluble  in  chloroform  and  the  other  not,  though  both  are  soluble 
in  alcohol. 


Examination  of  the  Petroleum  Ether  Extract. 

This  was  a  viscid,  brownish-yellow  colored  liquid  from  which, 
on  keeping  a  small  quantity  of  an  inactive,  needle-shaped  crystalline 
substance  separated  out,  having  1170  C.  as  its  melting-point,  the 
quantity  obtained  was  so  small  that  no  further  examination  was 
possible.  The  viscid  mass  also  contained  a  little  essential  oil,  which 
was  separated  by  extraction  with  alkalies  ;  the  rest  of  it  was  "  kalmegh 
resin,"  a  portion  of  which  was  extracted  by  first  making  it  alkaline 
with  caustic  potash  and  shaking  up  with  ether.  It  can  be  further 
extracted  with  ether  after  acidification  with  an  acid. 


Chloroform  Extract. 

This  contained  besides  chlorophyll  an  amorphous  white  substance 
and  very  little  of  a  bitter  substance,  the  former  of  which  separated 
out  on  concentrating  the  chloroform  extract.  Its  melting-point  is 
2210  C.  It  is  tasteless  and  insoluble  in  water  and  alcohol.  It  is 
unacted  upon  by  acids  and  alkalies. 


Extraction  of  the  Bitter  Principles. 

For  this  extraction  the  powdered  leaves  and  stems  were  ex- 
hausted in  a  percolator  with  alcohol,  almost  the  whole  of  which  was 
distilled  off.  The  thick,  viscid  mass  left  in  the  flask  was  then  sub- 
mitted to  steam  distillation.  Two  or  three  drops  of  an  essential  oil 
first  came  over ;  this  had  an  intensely  characteristic  odor  suggesting 
that  of  the  dried  plant.  The  distillation  continued  till  the  whole  of 
the  alcohol  was  distilled  off.  The  residue  remaining  in  the  flask 
separated  into  two  layers,  one  aqueous  and  the  other  solid ;  the 
former  when  allowed  to  cool  deposited  some  yellow  colored  crystals 
(bitter  a)  ;  the  latter  was  boiled  with  water  and  filtered  hot;  from 
the  filtrate  a  white  amorphous  precipitate  was  deposited  having  an 
extremely  bitter  taste  (bitter  b). 


352  Constituents  of  Andrographis  Paniculata.  {KmjJ™'  Jnf* 

Examination  of  the  Bitter  Principle  (A). 

This  was  purified  by  dissolution  in  alcohol  and  fractional  precipi- 
tation ;  the  process  was  repeated  three  times.  It  had  a  pale  yellow 
color.  When  a  little  of  the  substance  was  heated  in  a  test-tube  it 
diffused  a  very  fragrant  odor.   It  had  melting-point  of  2060  C. 

Strong  sulphuric  acid  produced  a  yellowish-brown  color.  With 
potassium  dichromate  and  sulphuric  acid  the  substance  at  first  gave 
a  deep  brown  (almost  black)  color,  attended  with  brisk  effervescence. 
After  a  time  the  effervescence  ceased  and  the  color  passed  to  grass- 
green. 

Strong  sulphuric  acid  containing  a  trace  of  nitric  acid  produced 
a  reddish-brown  color. 

Strong  sulphuric  acid  containing  ammonium  vanadate  produced 
brownish-red  color,  changing  to  green. 

In  strong  nitric  acid  the  substance  dissolved  readily,  the  solution 
acquiring  a  yellow  color. 

The  substance  is  very  soluble  in  ethyl  and  methyl  alcohol,  though 
not  to  the  above  extent  in  amyl  alcohol.  It  is  very  slightly  soluble 
in  chloroform  and  ether.  Benzene  and  petroleum  ether  do  not  dis- 
solve it  even  on  boiling. 

It  is  neither  an  alkaloid  nor  a  glucoside,  as  it  neither  contains 
nitrogen  nor  produces  a  reducing  sugar  after  hydrolysis.  It  can  be 
acetylated, — i.e.,  it  contains  hydroxyl  groups;  the  acetyl  derivative 
is  white  and  insoluble  in  water.    Its  melting-point  is  95  °  C. 

When  the  substance  was  added  to  a  solution  of  bromine  in 
chloroform  a  dark-colored  oil  separated  out;  on  washing  the  latter 
with  a  dilute  solution  of  potassium  carbonate  a  white  solid  substance 
was  left  behind.  This  was  the  bromo  derivative  of  the  bitter; 
the  direct  absorption  of  bromine  proves  the  presence  of  at  least  one 
double  bond.  The  melting-point  of  the  bromo  derivatives  would  not 
be  determined,  as  it  began  to  decompose  at  1200  C.  before  melting; 
at  1600  C.  it  was  a  liquid,  but  began  to  give  off  a  quantity  of  gas. 

0.0498  Gm.  of  the  bromo  derivative  gave  0.0160  Gm.  of  AgBr 
or  13.7  per  cent,  of  bromine.  Since  there  must  be  at  least  two 
atoms  of  bromine  in  the  molecule,  the  molecular  weight  is  1175  or 
some  multiple  of  it. 

0.1008  Gm.  of  the  bitter  analysis  gave  0.2521  Gm.  of  CO'2  and 
0.0763  Gm.  of  H20. 

Hence  C  68.2,  H  8.4. 


AmAu^"t*  igu™'}  Constituents  of  Andrographis  Paniculata.  353 
The  simplest  formula  is  C19H280;5. 

The  molecular  weight  of  the  bitter  principle  as  determined  from 
the  bromo-compounds  is  1015,  which  is  exactly  six  times  that  of 
the  empirical  formula. 

The  acetyl  derivative  gave  the  following  analytical  data : 

It  contains  1.74  per  cent,  of  water. 

0.0697  Gm.  of  it  gave  0.1863  Gm.  of  C02  and  0.05056  Gm.  of 
H20. 

Hence  C  76.2  H  8.06. 

Examination  of  the  Bitter  Principle  (B). 

It  was  a  white  amorphous  substance  having  an  extremely  bitter 
taste.  It  is  odorless,  and  its  melting-point  is  185 0  C.  It  is  practi- 
cally insoluble  in  cold  water.  When  a  little  of  the  substance  was 
boiled  for  a  long  time  with  water  the  latter  acquired  a  slightly  acid 
reaction.  It  is  soluble  in  alcohol  and  chloroform.  In  the  Pharma- 
cographia  of  Fluckiger  and  Hanbury  it  is  said  that  an  infusion 
gives  a  voluminous  precipitate  with  tannic  acid,  but  this  property 
was  altogether  found  to  be  absent.  Most  probably  in  the  former  case 
the  precipitate  was  due  to  the  presence  of  some  albuminous  matter. 
Sulphuric  acid  produces  an  orangish-yellow  color;  when  potassium 
dichromate  is  added  to  the  above  the  color  changes  as  one  to  yellow- 
green,  which  through  greenish-brown  finally  passes  to  deep  grass- 
green.  If  the  substance  be  mixed  with  potassium  dichromate  before 
the  addition  of  sulphuric  acid,  and  the  acid  then  added,  the  color 
first  produced  is  brown,  but  the  final  color  in  this  case  also  is  deep 
grass-green. 

Strong  sulphuric  acid  containing  a  trace  of  nitric  acid  gives  a 
brown  color. 

Strong  sulphuric  acid  containing  a  trace  of  ammonium  vanadate 
produces  a  brown  color,  changing  to  violet. 

Strong  nitric  acid  does  not  produce  any  change. 

0.409  Gm.  gave  0.0448  Gm.  of  H20  and  0.0930  Gm.  of  C02. 

C  62.01,  H<  14.88  and  O  23.01, 

The  formula  C19H5105  is  given  to  it,  for  which  the  theoretical 
values  are — 

C  62.24,  H  14.7  O  23.01. 
The  name  Kalmeghin  is  proposed  for  it. 

A  white  substance  separated  out  when  bitter  (b)  was  treated 
with  an  acid. 


354  On  Determination  of  Acetanilid.      {A^udT  ST™' 

This  was  washed  with  water  and  dried.  It  had  an  acid  reaction 
and  was  soluble  in  alkalies,  neutralizing  it.  As  it  was  derived  from 
Kalmeghin  the  name  Kalmeghic  acid  was  given  to  it. 

0.043  Gm.  gave  0.0699  Gm.  of  H20  and  0.2053  Gm.  of  CO.. 

Hence  C  75.23  H  10.4. 

The  formula  is  C14H2302. 

This  acid,  as  well  as  the  bitter  principle  (b),  gave  fluorescein 
test,  showing  the  presence  of  a  benzine  nucleus  with  two  adjacent 
side  chains. 

Chemical  Laboratory,  Presidency  College,  Bengal. 


ON  THE  DETERMINATION  OF  ACETANILID. 
By  Dr.  A.  Mirkin,  Cincinnati,  Ohio. 

The  determination  of  acetanilid  in  tablets  is  still  effected  by  an 
extraction  with  chloroform,  the  chloroform  being  collected  in  a 
tared  flask,  evaporated,  and  the  residue  dried  at  a  low  temperature 
and  weighed.  This  method  frequently  gives  low  results  on  account 
of  the  volatility  of  acetanilid,  and  very  often  it  is  not  applicable  at  all 
on  account  of  the  presence  of  other  ingredients  in  the  tablets  which 
are  also  soluble  in  chloroform. 

The  volumetric  method  adopted  by  the  Association  of  Official 
Agricultural  Chemists,  in  which  a  solution  of  potassium  bromide- 
bromate  is  used,  does  not  always  give  accurate  results,  and  it  seemed 
desirable  to  find  another  method  which  might  prove  successful  when 
other  methods  failed. 

Bay  and  Vignon  (Comptes  Rend.,  135,  507;  Centralblatt,  1902, 
ii,  1094)  determine  nitrous  acid  by  titrating  with  a  standard  solution 
of  aniline.  The  nitrous  acid  is  used  up  in  diazotizing  the  aniline. 
As  soon  as  the  nitrous  acid  is  gone  a  piece  of  potassium  iodide-starch 
paper,  with  which  the  solution  is  tested  from  time  to  time,  does  not 
turn  blue  any  more.  This  reaction  is  reversible,  and  one  can  titrate 
aniline  with  a  standardized  solution  of  sodium  nitrite.  By  convert- 
ing acetanilid  into  aniline  and  titrating  with  a  standard  sodium  nitrite 
solution,  we  have  a  quick  method  of  determination.  In  order  to 
obtain  correct  results  all  the  conditions  mentioned  below  must  be 
strictly  adhered  to. 


Am.  Jour.  Pharm. ) 
August,  1914.  / 


Vleminckx's  Solution. 


355 


One  gramme  of  acetanilid  is  boiled  for  four  hours  with  a  mixture 
of  one  part  sulphuric  acid  (sp.  gr.  1.84)  and  five  parts  water.  The 
solution  is  then  cooled  and  carefully  neutralized  with  sodium  bicar- 
bonate. HQ  is  then  added  (6  mol.  to  1  mol.  anilin)  and  the  flask 
is  cooled  to  — io°  by  throwing  in  pieces  of  ice  and  using  a  freezing 
mixture.  The  sodium  nitrite  is  then  slowly  added  from  a  burette 
with  thorough  shaking  of  the  flask  after  each  addition.  From  time 
to  time  the  solution  is  tested  with  potassium  iodide-starch  paper.  It 
frequently  happens  that  the  potassium  iodide-starch  paper  turns  blue 
even  when  there  is  unchanged  aniline.  This  is  due  to  the  low  tem- 
perature, which  causes  the  diazotizing  to  take  place  slowly.  One 
must  therefore  not  be  too  hasty  in  his  conclusions,  especially  at  the 
end,  but  wait  several  minutes  after  the  addition  of  sodium  nitrite 
before  applying  the  Kl-starch  paper  test. 

As  mentioned  above,  Bay  and  Vignon,  the  originators  of  this 
method,  should  be  given  full  credit.  I  have  only  adapted  their  method 
of  determining  aniline  to  the  determination  of  acetanilid. 


PREPARATION  AND  ANALYSES1  OF  VLEMINCKX'S 

SOLUTION.1 

By  Joseph  L.  Mayer. 

A  short  time  ago  two  samples  of  Vleminckx's  Solution  were  sub- 
mitted to  me  with  a  request  that  in  view  of  the  fact  that  the  color  of 
one  sample  was  markedly  different  from  the  other,  analyses  be  made 
to  ascertain  if  they  were  properly  prepared. 

Since  the  National  Formulary  only  contains  a  formula  for  the 
preparation,  and  various  pharmaceutical  authorities  consulted  made 
no  reference  to  a  standard,  it  was  necessary  to  make  samples  in  an 
effort  to  determine  how  the  solution  should  be  prepared  and  what 
the  strength  of  the  finished  product  should  be.  The  following  work 
was  therefore  undertaken. 

Referring  to  page  81,  3rd  edition  of  the  National  Formulary, 
we  found  that  "  Liquor  Calcis  Sulphuratse  " — "  Vleminckx's  Solu- 
tion " — was  directed  to  be  prepared  as  follows : 

Lime,  freshly  slaked  165  grammes. 

Sublimed  sulphur  250  grammes. 

Water,  a  sufficient  quantity  to  make  1000  grammes. 


1  Read  before  the  Kings  County  Pharmaceutical  Society,  May  12,  1914. 


356 


Vleminckx's  Solution. 


/Am.  Jour.  Phartu. 
(     August,  1914. 


Mix  the  slaked  lime  with  the  sulphur,  and  add  the  mixture  grad- 
ually to  1750  c.c.  of  boiling  water.  Then  boil  the  whole,  under  con- 
stant stirring,  until  it  is  reduced  to  1000  grammes,  strain,  and  having 
allowed  the  solution  to  become  clear  by  standing  in  a  well-stoppered 
bottle,  decant  the  clear  brown  liquid,  and  keep  it  in  completely  filled 
and  well-stoppered  bottles. 

We  accordingly  made  up  one-tenth  of  this  formula  by  taring  a 
600  c.c.  porcelain  evaporating  dish,  adding  175  c.c.  of  water  heating 
to  boiling  and  then  slowly  adding  the  mixture  of  freshly  slaked  lime 
and  sulphur,  constantly  stirring  while  heating  until  the  weight  was 
reduced  to  100  grammes.  The  material  was  then  decanted  into  a 
4  oz.  cork  stoppered  bottle,  allowed  to  stand  until  the  next  day, 
filtered  and  assayed  for  total  sulphur  by  the  following  method: 

14  Measure  10  c.c.  of  the  clear  sample  in  a  100  c.c.  measuring 
flask  and  fill  to  the  mark.  Analyze  10  c.c.  aliquots  of  this  solution. 
Treat  with  3  c.c.  of  saturated  solution  potassium  hydroxide  or  so- 
dium hydroxide  solution,  following  by  50  c.c.  hydrogen  peroxide 
free  from  sulphates.  Heat  on  the  steam  bath  for  one-half  hour 
exactly  and  then  acidify  with  hydrochloric  acid,  precipitate  with 
barium  chloride  in  the  usual  way  in  boiling  solution,  and  finally 
weigh  as  barium  sulphate."  Of  course  multiplying  the  weight  of 
barium  sulphate  by  the  proper  factor  gives  the  quantity  of  sulphur 
and  this  multiplied  by  100  gives  the  percentage. 

We  ran  blanks  on  the  reagents  and  determined  the  quantity  of 
sulphate  present,  which  was  then  deducted  from  that  found  in  the 
actual  analysis. 

This  is  Avery's  method,  and  is  suggested  by  the  Association  of 
Official  Agricultural  Chemists  for  the  analysis  of  lime-sulphur  dips 
and  lime-sulphur-salt  mixture  (U.  S.  Dept.  Agr.  Bureau  of  Chem- 
istry, Bui.  107,  rev.  page  34)  ;  it  is  an  extremely  accurate  and  simple 
one  which  in  our  hands  yielded  remarkably  close  duplicates. 

We  also  analyzed  the  sample  for  total  sulphur  irr  solution,  mono- 
sulphur  equivalent,  thiosulphate  sulphur,  sulphate  and  sulphite  sul- 
phur, total  sulphide  sulphur  and  total  lime  (CaO)  in  solution  follow- 
ing the  method  in  U.  S.  Dept.  Agr.  Bureau  of  Chemistry,  Bui.  162, 
page  29,  but  seeing  no  advantage  over  the  Avery  method,  employed 
that  in  all  our  analyses  and  simply  determined  the  total  sulphur,  of 
which  the  above  sample  showed  the  presence  of  10.838  grammes  in 
100  c.c.  of  solution. 


Am.  Jour.  Pharm.  ) 
August,  1914.  / 


Vleminckx's  Solution. 


357 


Another  100  gramme  lot  made  up  in  the  same  manner  contained 
14.581  grammes  of  total  sulphur  in  100  c.c.  of  solution. 

This  great  variation  in  results  indicated  difficulty  in  properly 
preparing  the  solution.  We,  therefore,  referred  to  the  direction  in 
the  N.  F.  and  found  it  directed  to  add  the  lime  and  sulphur  mixture 
"  gradually  to  1750  c.c.  of  boiling  water.  Then  boil  the  whole 
under  constant  stirring  until  it  is  reduced  to  1000  grammes ;"  this 
procedure  differs  from  mine  in  that  it  directs  the  water  to  be  heated 
to  boiling,  the  mixture  of  lime  and  sulphur  added  and  the  whole 
boiled  under  constant  stirring  until  the  weight  is  reduced  to  1000 
grammes. 

Another  100  gramme  lot  was  then  made  by  strictly  adhering  to 
these  directions  and  when  assayed  showed  the  presence  of  4448 
grammes  of  total  sulphur  in  100  c.c.  solution. 

My  original  reading  of  the  process  was  as  above  noted  to  heat 
the  water  to  boiling  and  then  while  the  water  was  still  on  the  fire 
to  gradually  add  the  lime  and  sulphur  under  constant  stirring  and 
boiling  until  the  proper  weight  was  produced,  whereas  the  last  prod- 
uct was  made  by  strictly  following  the  N.  F.  by  heating  the  water 
to  boiling,  taking  it  off  the  fire,  stirring  all  the  lime  and  sulphur  in, 
putting  it  back  on  fire,  stirring  and  heating  until  the  proper  weight 
was  attained. 

The  above  figures  clearly  indicated  that  the  wording  of  the  ma- 
nipulation in  the  N.  F.  was  faulty,  therefore  another  batch  of  100 
grammes,  employing  the  official  quantities,  was  made  by  taring  a  250 
c.c.  Erlenmeyer  flask,  adding  175  c.c.  of  water  heating  on  the  hot 
plate  until  boiling  and  then  adding  the  lime  and  sulphur  previously 
mixed  and  boiling  on  the  hot  plate  without  stirring  or  further  atten- 
tion until  the  weight  was  reduced  to  100  grammes,  transferred  to  a 
4  oz.  cork  stoppered  bottle,  allowed  to  stand  until  the  next  day, 
filtered  and  assayed. 

The  solution  contained  29.162  grammes  of  total  sulphur  in 
100  c.c. 

Another  lot  made  by  the  same  method  contained  29.593  grammes 
of  total  sulphur  in  100  c.c.  solution. 

These  figures  indicate  that  if  the  solution  is  prepared  in  a  flask 
the  product  will  practically  be  of  uniform  strength. 

It  is  true  the  N.  F.  does  not  state  whether  a  flask  or  evaporating 
dish  should  be  employed.  The  result  of  the  failure  to  specifically 
state  that  a  flask  or  similar  vessel  be  used  is  shown  by  the  analyses 


358  Preservatives  in  Syrup  of  Iron  Iodide.  {AbSj^5*  S£m' 

to  yield  preparations  of  indefinite  strength.  .  If  a  large  enough  flask 
is  not  at  hand,  vessels  which  are  deep  should  be  employed,  the  object 
being  to  avoid  too  rapid  evaporation  of  water,  as  the  proper  prepa- 
ration of  the  product  requires  several  hours. 

In  view  of  the  above  results  the  Committee  on  National  Formu- 
lary should  revise  the  wording  of  the  directions  for  the  preparation 
of  Vleminckx's  solution,  and  thus  insure  a  uniform  product.  Of 
course  if  thought  necessary  a  standard  could  be  fixed  for  the  prepa- 
ration and  a  method  of  assay  appended. 

I  would  take  this  opportunity  to  acknowledge  my  indebtedness 
to  my  assistant,  J.  H.  Wiener,  Ph.C,  for  assistance  rendered  in  the 
preparation  and  analyses  of  some  of  the  samples. 


A  NOTE  ON  THE  VALUE  OF  PRESERVATIVES  IN 
SYRUP  OF  IRON  IODIDE.1 

By  George  M.  Beringer. 

In  the  U.  S.  P.  8th  Revision,  diluted  hypophosphorous  acid  to 
the  extent  of  20  Cc.  to  1000  Gm.  has  been  added  to  this  syrup  as 
a  preservative.  Several  of  the  foreign  pharmacopoeias  have  used 
organic  acids  for  the  same  purpose,  the  Austrian  Pharmacopoeia 
directing  0.1  per  cent,  of  citric  acid,  the  Swiss  Pharmacopoeia  0.05 
per  cent,  of  citric  acid,  and  the  French  Pharmacopoeia  0.1  per  cent, 
tartaric  acid.  The  German  Pharmacopoeia,  the  British  Pharma- 
copoeia, the  Danish  Pharmacopoeia,  the  Swedish  Pharmacopoeia,  and 
the  Italian  Pharmacopoeia  do  not  direct  any  preservative,  dependence 
being  placed  upon  the  use  of  sufficient  sugar. 

In  order  to  test  out  the  relative  value  of  these  preservatives, 
six  samples  of  syrup  of  iron  iodide  were  prepared  on  October  15, 
1913.  In  all  of  these  the  official  process  and  manipulation  and 
percentage  of  iron  salt  and  sugar  were  carefully  followed.  These 
samples  were  preserved  in  my  laboratory  and  not  exposed  to  direct 
sunlight  for  several  months.  On  December  18th,  their  condition 
was  observed  and  noted.  Subsequently  these  samples  were  filed 
with  Chairman  Remington  and  preserved  in  his  laboratory  with 
the  other  pharmacopoeial  samples  until  a  few  days  ago,  when  I 
obtained  them  for  observation  of  the  further  changes  that  had 


1  Read  at  the  meeting  of  the  New  Jersey  Pharmaceutical  Association, 
Lake  Hopatcong,  June  17,  1914. 


AmAuoMi"t'  Si?111'}  Preservatives  in  Syrup  of  Iron  Iodide.  359 

taken  place.  In  the  tabulation  below  the  appearance  on  these  two 
dates  of  each  sample  is  noted: 

No.  1. — Proportions  of  the  U.  S.  P.  formula,  but  without  any 
preservative.  On  December  18th  this  sample  was  slightly  yellow. 
It  is  now  of  a  pale  green  color  and  appears  to  be  in  perfect  condition. 

No.  2. — U.  S.  P.  8th  formula  without  any  variation.  On  Decem- 
ber 18th  this  sample  was  very  pale  but  perfectly  clear.  It  was  noted 
that  the  green  color  had  gradually  faded  out  and  the  sample  was 
much  lighter  in  color  than  when  first  prepared.  This  is  in  accord- 
ance with  the  observations  on  this  formula  that  had  been  previously 
reported. 

This  sample  is  now  of  a  light  yellow  color  and  there  is  evidence 
of  some  change  in  the  sugar,  the  change  that  we  have  commonly 
considered  as  caramelizing  which  takes  place  in  the  presence  of 
hypophosphorous  acid  to  a  moderate  extent. 

No.  3. — Proportions  of  the  U.  S.  P.  with  the  addition  of  0.05 
per  cent,  of  tartaric  acid.  This  sample,  on  December  18th,  had 
assumed  a  distinct  yellow  color.  It  has  now  faded  until  it  is  almost 
colorless. 

No.  4. — Proportions  of  the  U.  S.  P.  formula  with  0.1  per  cent, 
of  tartaric  acid.  On  December  18th  this  sample  had  retained  the 
light  green  color  about  the  same  tint  as  when  first  prepared.  It  now 
shows  no  change  and  appears  to  be  in  perfect  condition. 

No.  5. — Proportions  of  the  U.  S.  P.  formula  with  the  addition  of 
0.05  per  cent,  of  citric  acid.  On  December  18th  this  sample  was  of 
a  very  light  green  color  and  preservation  appears  to  have  been  per- 
fect.   It  now  shows  no  further  change. 

No.  6. — Proportions  of  the  U.  S.  P.  formula  with  the  addition 
of  0.1  per  cent,  of  citric  acid.  On  December  18th  this  sample  had 
retained  its  original  pale  green  color,  and  at  this  time  preservation 
appears  to  have  been  perfect. 

Conclusions. — If  syrup  of  iron  iodide  is  carefully  made  and  with 
the  proper  amount  of  sugar,  no  preservative  whatever  is  needed. 
However,-  to  overcome  the  careless  manipulation  on  the  part  of  some 
druggists,  it  has  been  deemed  advisable  to  add  a  preservative. 
Hypophosphorous  acid  has  the  advantage  of  a  reducing  value  which 
is  not  possessed  by  the  organic  acid  suggested  for  this  purpose.  It 
has,  however,  the  disadvantage  that  in  the  strength  directed  it  will 
act  upon  sugar  in  strong  solutions  and  darken  the  syrup.  This  could 
be  overcome  by  substituting  glycerin  for  a  portion  of  the  sugar 
directed  in  the  formula. 


360 


Petrolatum  Liquidum,  U.  S.  P.  VI IL  {K\*™£v&™' 


PETROLATUM  LIQUIDUM,  U.  S.  P.  VIII  (PARAFFINUM 
LIQUIDUM),  WHITE  MINERAL  OIL. 

By  S.  L.  Hilton. 

The  U.  S.  P.  VIII  provides  that  this  substance  shall  conform  to 
the  following  description : 

A  mixture  of  hydrocarbons,  chiefly  of  the  methane  series,  obtained 
by  distilling  off  most  ,of  the  higher  and  more  volatile  portions  from 
petroleum  and  purifying  the  liquid  residue. 

A  colorless,  or  very  slightly  yellowish,  oily,  transparent  liquid 
without  odor  or  taste,  but  giving  off,  when  heated,  a  faint  odor  of 
petroleum. 

Sp.  gr.  .870  to  .940  at  25 0  C.  Tests  as  to  solubility,  acid  impuri- 
ties, fixed  oils  or  fats,  either  animal  or  vegetable,  and  readily  carbon- 
izable  impurities. 

It  is  proposed  for  the  U.  S.  P.  IX  to  change  the  official  title  to 
Paraffinum  Liquidum.  This  seems  to  be  wise  and  in  conformity 
to  modern  standards.  The  description,  allowing  a  very  slight  yellow 
color,  is  a  mistake,  as  there  is  no  difficulty  in  obtaining  a  colorless  oil 
except  the  oils  of  this  kind  that  are  produced  in  this  country.  The 
new  requirement  which  requires  that  it  shall  be  free  from  fluorescence 
is  proper  and  not  unnecessarily  exacting. 

From  a  careful  study  of  a  number  of  samples  of  white  mineral  oil, 
obtained  from  various  sources,  the  appended  table  shows  that  the 
official  requirements  can  be  met  without  much  difficulty ;  it  is  further 
demonstrated  that  an  oil  that  is  usually  above  the  sp.  gr.  .870  will 
show  more  or  less  paraffin  when  subjected  to  a  temperature  of  — 40 
C,  yet  in  the  table  two  samples,  each  of  the  sp.  gr.  of  .875,  remained 
perfectly  clear  after  being  subjected  to  this  temperature  for  eight 
hours.  It  is  therefore  evident  that  in  the  process  of  purification 
chilling  was  not  thorough  or  carried  on  for  a  sufficient  length 
of  time,  and  the  final  filtration  was  not  performed  at  the  same 
temperature.  The  desire  to  have  as  heavy  oil  as  possible  for  internal 
administration,  as  recommended  by  Dr.  Lane,  of  London,  is  no  doubt 
accountable  for  such  a  large  number  of  samples  with  a  specific 
gravity  lower  than  .875  becoming  opaque  or  milky  at  this  temperature. 

With  proper  manipulation  and  care  an  oil  of  the  sp.  gr.  .8755 
should  show  no  separation  of  paraffin  on  chilling.  Some  standard 
covering  this  point  should  be  provided ;  that  is,  a  minimum  specific 


A  August,"  i9i?m'}  Petrolatum  Liquidum,  U.  S.  P.  VIII.  361 

gravity  that  will  show  no  separation  of  paraffin  when  the  oil  is  sub- 
jected to  a  temperature  of  at  least  o°  C. 

None  of  the  samples  showed  an  admixture  of  fixed  oils  or  fats, 
either  animal  or  vegetable.  The  test  is  one  that  must  be  carefully 
applied,  or  an  accident  will  follow.  The  neutralizing  of  the  alkali 
with  strong  sulphuric  acid,  after  digestion,  is  violent  unless  it  is 
added  very  slowly. 

The  results  of  the  sulphuric  acid  test  are  most  interesting,  show- 
ing almost  every  shade  of  brown,  and  in  several  cases  the  only  layer 
became  opaque  and  colored  and  not  conforming  to  the  requirements 
of  the  pharmacopoeia  or  the  standard  as  given  in  the  British  or 
German  Pharmacopoeias. 

As  to  the  internal  administration  of  paraffin  oil,  a  number  of 
specialists  of  this  city  have  used  it  for  several  years.  The  principal 
method  followed  by  them  is  to  administer  from  15  to  50  Cc.  at  bed- 
time; in  obstinate  cases  of  constipation  15  Cc.  administered  about 
one  hour  before  meals,  so  as  to  avoid  interfering  with  the  process 
of  digestion.  With  these  methods  of  administration  good  results 
have  been  produced.  There  are,  however,  many  cases  where  com- 
plaints have  been  made  that  the  oil  will  pass  out  of  the  intestinal 
tract  involuntarily,  very  much  to  the  discomfort  of  the  patient,  even 
when  given  in  very  small  doses.  This  trouble  seems  to  be  more  fre- 
quent with  the  administration  of  one  of  the  popular  brands  of  the 
market  which  shows  a  specific  gravity  of  less  than  .860.  To  a  certain 
extent  this  may  account  for  the  growing  demand  for  heavier  paraffin 
oils. 

Paraffin  oils  of  a  specific  gravity  of  .880  or  more  are  rather  more 
difficult  of  administration  than  those  of  .870  to  .875 ;  they  adhere  to 
the  mouth  very  closely,  and  to  some  are  disagreeable  and  suggestive 
of  castor  oil. 

An  oil  aromatized  or  flavored  with  some  essential  oil  or  combina- 
tion of  oils  seems  to  be  growing  in  demand.  I  submit  ten  samples, 
all  of  which,  no  doubt,  to  some  would  be  agreeable.  Personally, 
peppermint  seems  to  be  the  most  pleasant  and  agreeable ;  cardamon 
a  close  second.  No  doubt,  many  would  prefer  spearmint,  owing  to 
the  chewing-gum  craze. 

The  flavoring  of  paraffin  oils  must  be  done  with  care.  From  5  to 
25  drops  of  an  essential  oil,  according  to  which  is  used,  will  be  found 
sufficient  for  500  Cc.  While  this  small  amount  may  not  give  a  pre- 
dominant odor,  it  must  be  remembered  that  the  dose  administered, 


362 


Petrolatum  Liquidum.  U.  S.  P.  VIII.  { AmAuJgZ't  EST' 


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AnAu"u"t*  SS**"}  Physiological  Characteristics  of  Acetylene.  363 

15  to  60  Cc.,  will  be  sufficient  to  give  a  fairly  pronounced  taste.  The 
samples  submitted  contain  in  each  500  Cc.  the  following  amounts  of 
essential  oils  :  Almond,  15  drops  ;  cloves,  10  drops  ;  anethol,  10  drops  ; 
cinnamon,  5  drops  ;  peppermint,  15  drops  ;  spearmint,  15  drops  ;  sweet 
birch,  25  drops ;  wintergreen,  25  drops ;  and  aromatic,  using  the  oils 
constituting  spirit  aromaticus  comp.,  15  drops. 

Another  interesting  phase  of  the  examination  is  the  various 
prices  charged  for  these  paraffin  oils,  tlfose  with  fancy  coined  names 
commanding  very  much  more  than  other  oils  on  the  open  market,  and 
all,  or  nearly  all,  coming  from  the  same  source  and  possibly  the  same 
importer.  As  has  been  pointed  out  by  Mr.  Wilbert,  the  better  or  fine 
grades  come  from  Russia,  hence  the  name  Russian  Mineral  Oil;  the 
American  oil  usually  has  a  fluorescence,  slightly  yellow  in  color,  and 
a  more  pronounced  petroleum  odor  when  heated.  The  best  grades  of 
Russian  oil  can  be  purchased  for  about  80  cents  a  gallon,  while  those 
with  trade  or  coined  names  will  cost  from  40  to  60  cents  a  pint. 

The  pharmacist  should  be,  and  is,  able  to  supply  physicians  and  his 
patients  with  an  oil  of  high  quality,  reasonable  in  price,  and  should 
avail  himself  of  the  present  opportunity.  An  oil  of  at  least  the  sp.  gr. 
.8750  that  is  colorless,  tasteless,  and  free  from  fluorescence,  that  will 
not  show  more  than  a  pale  brown  color  with  the  sulphuric  acid  test, 
free  from  admixture  with  animal  or  vegetable  oils,  and  remains  clear 
when  subjected  to  a  temperature  of  o°  C.  for  four  hours,  seems  to  be 
the  oil  most  desired  and,  if  demanded,  can  readily  be  obtained. 


THE  PHYSIOLOGICAL  CHARACTERISTICS  OF  ACETY- 
LENE, WITH  RESPECT  TO  ITS  USE  IN  MINING.*  ■ 

By  E.  E.  Smith,  Ph.D.,  M.D. 

Like  every  other  step  in  the  progress  of  civilization,  the  use  of 
acetylene  involves  certain  readjustments  of  previous  notions.  In 
the  art  of  illumination,  these  problems  of  adjustment  have  been 
particularly  definite  and  impelling.  Thus,  the  pine  knot  did  not  give 
way  to  the  candle,  probably,  without  anxious  consideration  of  the 
danger  of  spattering,  soot  making,  and  extinction  by  drafts.  Many 

*  A  paper  read  at  a  meeting  of  the  International  Acetylene  Association, 
late  in  1913,  for  a  report  of  which  the  Quarterly  is  indebted  to  Secretary 
A.  C.  Morrison,  42d  St.,  Building,  New  York.  Reprinted  from  the  School 
of  Mines  Quarterly,  vol.  xxxv.,  1914,  pp.  143-153. 


364  Physiological  Characteristics  of  Acetylene.  jA^uJg°ust'  iP9Hrm* 

years  of  careful  study  were  needed  to  solve  the  last  of  the  dangers 
involved  in  the  use  of  kerosene,  while  the  difficulties  connected 
with  illuminating  gas  and  electricity  are  still  with  us.  This  paper 
will  be  limited  to  the  problems  of  adjustment  presented  by  the  use  of 
acetylene  as  an  illuminant. 

This  leads  us  at  once  to  the  inquiry,  Is  acetylene  a  direct  poison? 
The  answer  is  no.  This  question  is  asked  with  some  seriousness, 
however,  because,  on  the  one  hand,  of  the  notoriously  toxic  action 
of  common  illuminating  gas,  due  to  the  carbon  monoxide  which 
enters  so  largely  into  its  composition,  by  reason  of  which  the  mind 
of  the  inquirer  is  already  not  only  prepared  to  believe  that  acety- 
lene is  poisonous,  but,  in  fact,  in  some  instances  has  that  idea  rigidly 
implanted  there.  It  is  further  asked  with  seriousness,  because,  in 
the  literature  of  the  subject, -we  find  some  views  that  it  is  poisonous. 
Early  writers  declared  that  it  combined  with  the  blood  and  had 
a  marked  poisonous  effect,  like  carbon  monoxide. 

Any  gas,  when  it  replaces  air,  if  incapable  of  supporting  respira- 
tion, is  injurious  and  even  fatal,  not  because  it  is  poisonous  but 
because  it  deprives  the  body  of  oxygen.  Because  of  this,  acetylene 
is  capable  of  doing  injury.  If  it  accumulates  in  some  small,  unventi- 
lated  space,  like  the  cabin  of  a  boat,  it  is  entirely  capable  of  shutting 
off  the  supply  of  air,  of  preventing  respiration  and  hence  causing 
harm  and  even  death.  It  suffocates  because  it  is  incapable  of 
supplying  oxygen,  without  which  man  cannot  live. 

When  acting  in  this  way,  acetylene  is  not  a  direct  poison ;  it  does 
not  do  anything  to  the  body  to  injure  it.  It  does  harm  only  in- 
directly, by  withholding  air.  The  recognition,  then,  of  injury  by 
suffocation  throws  no  light  on  our  inquiry  whether  it  is  a  direct 
poison.  The  presence  of  common  illuminating  gas  in  air,  even 
to  the  amount  of  a  fraction  of  a  per  cent.,  is  distinctly  injurious 
and  may  even  be  fatal,  though  such  air  contain  an  abundance  of 
oxygen.  The  carbon  monoxide  contained  in  illuminating  gas  enters 
the  blood  through  the  lungs  and  attaches  itself  strongly  to  the  color- 
ing matter  of  the  blood,  rendering  it  incapable  of  taking  up  the 
oxygen  of  air  though  the  air  contain  oxygen  in  ample  amount.  Thus 
death  supervenes  not  because  the  body  is  denied  oxygen  but  because, 
through  the  fixation  of  the  coloring  matter  of  the  blood,  it  has  lost 
its  capacity  to  use  oxygen.  Has  acetylene  this  or  any  other  directly 
poisonous  action?  Some  early  observers  said  it  had.  They  found 
fixation  of  haemoglobin  quite  similar  to  that  of  carbon  monoxide 


ADAugu"t'  mT™' }  Physiological  Characteristics  of  Acetylene.  365 

and  accordingly  declared  acetylene  a  poison.  Moreover,  it  seemed 
to  exercise  the  action  of  a  direct  poison  on  animals. 

This  was  ascertained  before  acetylene  was  regularly  produced 
from  carbide.  The  acetylene  of  that  date  was  made  by  the  incom- 
plete combustion  of  coal-gas,  whence  more  or  less  carbon  monoxide 
was  present  in  the  acetylene  obtained,  thus  accounting  for  some 
degree  of  toxic  action  of  the  acetylene  examined.  Carbon  monoxide 
is  the  poison  of  common  illuminating  gas. 

With  the  discovery  of  carbide  and  its  use  for  the  production  of 
acetylene,  all  of  this  has  been  changed,  it  is  now  found  that  acety- 
lene from  carbide  does  not  contain  carbon  monoxide,  that  it  does 
not  have  the  property  of  fixing  haemoglobin,  and  that  it  does  not 
rob  the  blood  of  its  capacity  to  take  up  oxygen  from  the  air  and 
carry  it  into  the  tissues.  Hence  the  old  allegation  that  acetylene 
is  a  poison  because  it  deprives  the  blood  of  its  oxygen-carrying 
capacity  is  no  longer  justified. 

Another  poisonous  product  sometimes  present  in  the  acetylene 
made  by  the  old  combustion  process  was  hydrocyanic  acid.  Never 
in  large  quantities,  it  yet  is  so  toxic  that  we  can  fully  appreciate  its 
effect.  It  is  not  present  in  the  carbide  acetylene  and  so  may  be 
dismissed  from  consideration.  Another  charge  that  is  no  longer 
justified  is  that  acetylene  is  a  poison  because  of  the  presence  of 
phosphine  as  an  impurity.  This  forms  when  carbide  is  made  from 
limestone  containing  phosphate,  which  is  reduced  by  the  action  of 
the  coke.  The  selection  of  limestone  free  from  phosphate  has  prac- 
tically obviated  this  impurity  and  any  poisonous  effect  of  the  acetylene 
consequent  thereto.  Indeed,  the  present  day  product  may  be  said 
to  avoid  the  pitfalls  of  impurities  so  that  its  effect  is  determined 
by  the  characteristics  of  acetylene  itself.  We  may  consider  then 
whether  acetylene,  as  such,  is  or  is  not  a  direct  poison. 

My  present  observations  have  been  directed  to  the  inquiry  whether 
it  produced  noticeable  effect  on  human  subjects  when  present  in 
increasing  amounts  up  to  2^2  per  cent,  during  a  period  of  2^  hours. 
To  this  end,  four  men,  including  myself,  were  enclosed  in  a  room 
of  about  800  cu.  ft.  capacity ;  at  the  beginning  and  four  times 
subsequently  at  intervals  of  a  half -hour,  acetylene  was  liberated  in 
the  room  bv  throwing-  450  grams  of  carbide  into  an  open  tub  of 
water,  this  corresponding  to  the  liberation  of  4  cu.  ft.  of  acetylene 
each  time;  that  is,  20  cu.  ft.  in  all,  2T/2  per  cent,  of  the  capacity  of  the 
room. 


1 


366  Physiological  Characteristics  of  Acetylene.  {Am(Ug™tr'  SJj™1' 

To  eliminate,  as  far  as  possible,  the  mental  effect  of  the  environ- 
ment, the  subjects  were  engaged  in  playing  a  game  of  cards.  They 
were  interrupted  only  long  enough  to  take  readings  of  their  blood 
pressures,  at  half-hour  intervals.  The  results  of  the  experiment  were 
quite  negative.  The  game  was  continued  throughout  the  period, 
excepting  as  noted.  The  blood  pressure  remained  constant  with 
one  subject  and  was  very  slightly  lowered  from  the  inactivity  with 
two,  and  absolutely  no  effect  was  noted  that  could  be  ascribed  to  any 
poisonous  or  other  action  of  the  acetylene.    It  was  without  effect. 

This  same  result  has  been  obtained  in  experiments  on  animals. 
In  such  amounts  as  used  in  the  above  experiments  there  is  no  effect. 
Indeed,  acetylene  may  be  increased  up  to  20  per  cent,  and,  if  the 
mixture  is  so  made  as  not  to  reduce  the  amount  of  oxygen,  animals 
may  be  left  in  the  atmosphere  for  some  time,  an  hour  or  more,  and 
will  only  become  drowsy,  from  which  they  quickly  recover  when 
removed  into  ordinary  air. 

With  very  large  quantities,  or  with  20  per  cent,  admixtures  act- 
ing for  a  longer  time,  the  degree  of  drowsiness  is  increased.  That 
is  to  say,  the  effect  of  acetylene  in  large  doses  is  that  of  a  narcotic, 
producing  loss  of  consciousness  in  proportion  to  its  degree  of  action. 
When  this  action  is  pushed  to  a  fatal  termination,  the  final  effect  is 
upon  the  breathing  centre,  inhibiting  its  action  and  so  producing 
death. 

It  thus  appears  that  carbide  acetylene  is  not  poisonous  in  the 
sense  that  common  illuminating  gas  is,  and  that  in  large  quantities, 
acting  for  some  time,  it  produces  a  narcotic  action.  In  respect  to 
its  toxicity,  it  presents  no  problem  of  adjustment  under  ordinary 
conditions.  It,  of  course,  may  not  replace  in  large  degree  the  atmos- 
phere we  breathe,  but  otherwise  no  poisonous  action  need  be  antici- 
pated. 

A  number  of  interesting  problems  are  presented  in  connection 
with  the  use  of  the  acetylene  lamp  as  an  illuminant  in  mines.  I  do 
not  refer  to  those  conditions  where  explosive  gases  are  present, 
where  protection  from  explosions  is  obtained  through  the  use  of  the 
Davy  lamp  in  some  of  its  modifications,  but  to  that  large  number 
of  mines  which  are  regularly  illuminated  by  the  naked  flame.  For 
this  purpose,  the  miner's  oil  lamp  has  been  used  for  many  years, 
It  is  light  in  weight,  but  its  illuminating  capacity  is  strikingly  low 
and,  moreover,  is  obtained  at  the  expense  of  a  smoking-out  process 
that  is  amazing.   It  is  a  tribute  to  the  miner's  endurance  that  in  the 


^usust*  fm™' }  Physiological  Characteristics  of  Acetylene.  367 

past  he  has  accomplished  so  much  under  the  conditions  of  poor 
illumination  and  soot-laden  atmosphere  which  the  use  of  the  oil 
lamp  has  meant.  The  use  of  the  miner's  acetylene  lamp  affords  an 
illumination  that  is  wonderfully  efficient  and  entirely  soot- free.  Its 
use  raises  some  questions  that  we  may  answer  at  this  time.  Before 
considering  these,  let  us  look  at  some  of  the  problems  which  the 
miner  has  to  face,  upon  which  the  choice  of  an  illuminant  may  have 
some  bearing.  Of  first  importance  is  the  composition  of  the  air  which 
he  breathes. 

For  our  present  purpose  we  may  regard  the  atmospheric  air  as 
a  mixture  of  21  parts  of  oxygen  and  79  parts  of  inert  gas,  mostly 
nitrogen.  It  is  the  oxygen  that  supports  life.  The  proportion  of 
oxygen  may  be  diminished  to  a  certain  extent  without  noticeable 
effect,  especially  if  the  difference  is  made  up  by  inert  nitrogen.  Under 
these  conditions  a  reduction  to  14  per  cent,  produces  little  or  no 
physiological  effect.  When  the  reduction  reaches  12  per  cent., 
there  is  apt  to  be  slightly  deeper  breathing,  while  10  per  cent,  is  an 
amount  distinctly  below  what  is  physiologically  advisable.  Seven 
per  cent,  may  be  regarded  as  the  fatal  point.  It  is  an  amount  too 
small  to  support  the  life  of  animal  or  man  for  any  considerable 
time.  It  must  be  kept  in  mind  that  these  figures,  10  per  cent,  the 
physiological  insufficiency  and  7  per  cent,  the  fatal  point,  are  for 
oxygen  with  inert  nitrogen,  and  without  the  admixture  of  poisonous 
gases. 

There  is  always  present  in  atmospheric  air  a  small  amount  of 
carbon  dioxide  gas,  commonly  known  as  carbonic  acid.  This  amount 
is  very  small,  ordinarily  not  over  5  parts  in  10,000.  It  is  a  product 
of  the  combustion  of  organic  matter  and  is  present  in  air  exhaled 
from  the  body  in  breathing.  As  we  shall  see  later,  it  is  also  a  con- 
stituent of  mine  gases  and  so  is  of  particular  interest  to  us.  I  will 
call  attention  to  what  happens  when  it  is  added  to  the  air. 

To  answer  this  question  I  have  myself  made  direct  observations. 
The  apparatus  employed  was  a  closed  cabinet,  the  inside  measure- 
ments of  which  were  approximately  67  x  30  x  69  in.,  having  a  capa- 
city of  80  cu.  ft.  It  was  provided  with  a  sliding  door.  Into  the 
top  a  pipe  entered  and  connected  with  three  "  sprays,"  one  in  each 
third  of  the  top.  Through  this  system  gases  were  introduced.  There 
was  a  small  sample  tube,  easily  movable,  so  that  gas  was  withdrawn 
from  any  position  desired  within  the  cabinet,  which  was  connected 
outside  with  (a)  an  exhaust  bottle  for  withdrawing  residual  air 


368  Physiological  Characteristics  of  Acetylene.  { A^Ugu"t'  SE**' 

from  the  tube;  and  (b)  a  gas-sampling  tube.  Collections  were  made 
over  mercury  and  analysis  was  made  over  mercury  in  a  Hempel 
apparatus.  The  cabinet  was  tightly  built,  but  not  sufficiently  so 
to  prevent  escape  of  air  sufficient  to  equalize  the  pressure  without 
and  within  the  cabinet  when  gas  was  introduced.  A  movable  electric 
fan  within  the  cabinet  was  adapted  to  produce  motion  of  the  air. 

When  carbon  dioxide  was  mixed  with  atmospheric  air,  it  was 
noted  that  such  mixture  produced  an  increased  rate  of  respiration, 
even  when  the  proportion  of  carbon  dioxide  was  small.  Rabbits 
and  guinea-pigs  showed  a  marked  increase  when  as  much  as  4  to  5 
per  cent,  of  carbon  dioxide  was  present.  With  increasing  proportions 
respirations  became  deep  and  labored,  frequently,  as  was  observed 
in  guinea-pigs,  reaching  a  condition  of  diaphragmatic  spasm.  Loss 
of  muscular  power  developed  so  that,  with  guinea-pigs,  ability  to 
support  the  body  was  lost  when  the  carbon  dioxide  reached  20  to  25 
per  cent.  These  symptoms  developed  irrespective  of  whether  lamps 
were  burnt  in  the  same  atmosphere.  With  rabbits,  when  lamps 
were  burning,  loss  of  muscular  power  appeared  with  the  same  pro- 
portion of  carbon  dioxide  as  with  guinea-pigs,  but  in  a  single  obser- 
vation made  without  lamps,  the  loss  of  power  appeared  when  the 
carbon  dioxide  had  reached  36  per  cent.  No  effort  was  made  to 
determine  the  percentage  of  carbon  dioxide  that  would  produce  death, 
as  it  was  believed  that  the  proportion  producing  loss  of  muscular 
power  represented  the  limit  of  possible  tolerance.  It  may  be  noted, 
however,  that  in  the  experiment  carried  to  36  per  cent,  carbon  dioxide, 
the  rabbit  quickly  recovered,  two  guinea-pigs  recovered  somewhat 
slowly,  and  one  guinea-pig  died,  when  the  animals  were  removed 
into  fresh  air.  Thus  it  appears  that  even  with  guinea-pigs,  the  fatal 
carbon  dioxide  proportion  is  not  much  if  any  below  36  per  cent, 
while  the  carbon  dioxide  warning  point  is  not  above  4  to  5  per  cent., 

To  test  the  effect  of  carbon  dioxide  on  man,  ioJ/2  cu.  ft.  of  carbon 
dioxide  were  passed  into  the  cabinet,  when  a  young  man  entered,  the 
door  being  opened  for  that  purpose  and  quickly  closed.  After 
entering,  the  fan  was  started.  The  rate  of  respiration  at  once  rose 
from  18  to  48,  being  deeper  and  labored.  He  almost  immediately 
complained  of  feeling  dizzy.  At  the  end  of  2^  min.  there  was  a 
feeling  of  impending  loss  of  consciousness.  A  sample  of  the  air 
mixture  was  at  once  taken  and  at  the  end  of  3  min.  the  man  came 
out.  His  respiration  quickly  returned  to  normal,  but  his  face  was 
flushed  and  he  complained  for  several  hours  of  a  slight  frontal 


ADAugust  im.m' }  Physiological  Characteristics  of  Acetylene.  369 

headache.  Analysis  of  the  sample  showed  7  per  cent,  of  carbon 
dioxide.  The  experiment  indicated  that  with  man  the  warning  point 
is  reached  below  7  per  cent,  of  carbon  dioxide. 

Such  experiments  lead  to  the  following  general  conclusions  re- 
garding the  physiological  effects  of  increasing  proportions  of  carbon 
dioxide.  There  is  increase  in  the  rate  of  breathing  which,  with 
3  per  cent,  dioxide,  has  become  so  marked  that  it  gives  unquestioned 
warning  to  the  subject  that  some  unusual  condition  of  the  air  is 
rendering  it  unsuited  for  breathing.  We  may  call  this  the  physio- 
logical warning  point  for  carbon  dioxide.  When  the  concentration 
reaches  8  to  10  per  cent.,  the  breathing  is  not  only  rapid  but  has 
become  very  labored,  a  condition  termed  dyspnea.  Beyond  15  per 
cent.,  further  concentration,  instead  of  increasing  respirations,  de- 
creases them  and  the  animal  becomes  narcotized,  quite  as  though 
a  substance  like  chloroform  had  been  administered.  At  a  concen- 
tration beyond  35  per  cent,  the  narcosis  becomes  fatal. 

I  have  gone  into  the  influence  of  oxygen  decrease  and  of  carbon 
dioxide  increase  on  breathing  and  on  life  because  these  are  condi- 
tions that  may  be  presented  by  the  air  in  mines.  Moreover,  the  oil 
lamp  has  been  relied  upon  to  indicate  to  the  miner  whether  or  not 
the  mine  air  is  fit  to  breathe,  air  that  sustains  the  flame  being  regarded 
as  safe  and  air  that  extinguishes  the  flame  as  unsafe  to  breathe. 

The  disadvantages  of  the  oil  lamp  are  all  too  apparent.  Its  dingy 
light  limits  the  working  capacity  of  the  miner,  due  to  poor  illumina- 
tion. Aside  from  working  capacity,  the  miner  is  not  so  well  able 
to  see  the  elements  of  danger  presented  by  weakness  in  overhanging 
strata  or  structures.  An  even  greater  disadvantage  is  the  production 
of  soot  by  the  flame.  This  both  adds  to  the  personal  discomfort, 
already  great,  and  also  to  the  danger  of  dust  explosions  by  addition 
of  the  soot  to  the  dust-laden  atmosphere.  These  conditions  render 
an  illuminant  that  is  brilliant  and  soot-free  a  very  great  advantage. 
The  acetylene  lamp  supplies  such  an  illuminant  in  an  admirable 
manner.  In  connection  with  its  use  it  is  desirable  to  determine  its 
relation  to  composition  of  mine  air,  so  that  the  miner  may  know  in 
what  way  and  to  what  extent  it  replaces  the  oil  lamp  as  an  index 
of  safety.  That  is  to  say,  we  have  here  a  problem  of  adjust- 
ment to  which  it  is  important  to  give  a  correct  and  definite  answer. 

First,  then,  let  us  consider  the  variations  in  composition  that 
may  be  presented  by  mine  air.  Because  of  the  limitations  of  access 
of  outside  air  and  especially  because  of  the  formation  of  gases  in 


370  Physiological  Characteristics  of  Acetylene.  {AuiUgu"t' 


Pharm. 
1914. 


mines,  mine  air  may  present  a  considerable  departure  from  the 
composition  of  outside  air. 

All  ordinary  foreign  gases  were  known  to  the  early  miners  as 
"  damps/'  from  the  German  damf,  meaning  vapor,  the  specific  desig- 
nation being  indicated  by  an  individual  prefix.  Thus,  the  gas  charac- 
terized by  its  tendency  to  extinguish  the  flame  was  called  black- 
damp,  or,  since  it  tends  to  produce  suffocation,  choke-damp;  the 
damp  producing  increased  brilliancy  of  light,  white-damp ;  that  with 
a  marked  stink,  stink-damp ;  that  which  readily  took  fire,  fire-damp ; 
the  gas  resulting  from  burning  or  explosion,  after-damp,  etc.  These 
names  were  applied  long  before  the  composition  of  the  respective 
gases  was  known.  In  consequence  of  the  indefinite  basis  of  the 
classification,  an  individual  name  was  in  many  instances  applied  to 
mixtures  that  presented  wide  variation  in  composition. 

Black-damp,  on  chemical  analysis,  has  ordinarily  proved  to  be 
a  mixture  of  carbon  dioxide  and  nitrogen,  the  proportion  of  carbon 
dioxide  varying  from  very  little  up  to  15  per  cent,  or  perhaps  excep- 
tionally 20  per  cent.  As  it  is  always  mixed  with  more  or  less  air, 
a  corresponding  amount  of  oxygen  is  present.  Other  gases,  such  as 
methane  (fire-damp),  carbon  monoxide  (white-damp),  hydrogen- 
sulphide  (stink-damp),  also  water  vapor,  may  be  present  in  greater 
or  less  amount. 

We  may  well  ask,  then,  what  the  name  black-damp  indicates. 
Does  it  mean  carbon  dioxide,  which  is  the  characteristic  constituent ; 
does  it  mean  the  carbon  dioxide-nitrogen  mixture;  is  it  the  carbon 
dioxide-nitrogen-air  mixture;  or  is  it  the  combination  of  any  of  these 
with  other  gases  that  are  present  in  the  mine  air?  Unfortunately, 
there  has  been  no  unanimity  of  usage  in  regard  to  this  term,  it  having 
been  used  by  different  writers  in  almost  every  one  of  the  above  pos- 
sible meanings. 

If  we  were  to  establish  anew  the  definition  of  the  term,  it  would 
be  doubtless  wise  to  adopt  a  scientific  meaning.  As  the  matter  stands, 
our  meaning  should  be  decided  by  priority,  which  is  that  black-damp 
is  not  simply  carbon  dioxide  but  rather  a  mixture  of  that  with  nitro- 
gen in  varying  proportions,  but  we  must  not  forget  the  different 
usages  of  individual  authors. 

Our  problem  is :  How  does  the  admixture  of  black-damp  modify 
the  respirability  of  mine  air  and  how  is  this  indicated  by  the  oil  and 
acetylene  flames?  It  requires  no  facts  other  than  those  now  before 
us  id  appreciate  that  it  affects  respirability  in  two  ways.    It  dimin- 


ADAuiuU8t'  i9hi4rm'}  Physiological  Characteristics  of  Acetylene.  371 

ishes  the  proportion  of  oxygen  which,  if  reduced  to  10  per  cent., 
would  be  unphysiological  and  to  7  per  cent.,  fatal ;  and  it  increases 
carbon  dioxide  which,  when  present  to  the  amount  of  3  to  4  per  cent., 
would  produce  marked  increase  in  the  rate  of  breathing. 

As  to  when  the  change  in  composition,  especially  the  carbon 
dioxide  increase,  is  indicated  by  the  particular  flames,  has  been  the 
subject  of  personal  experimental  observations.  The  cabinet  employed 
in  the  experiment  previously  described  was  used.  In  the  earlier 
experiments  with  carbon  dioxide,  this  gas  was  fed  into  the  cabinet 
without  previous  admixture  with  air ;  in  the  later  ones  both  air  and 
carbon  dioxide  were  fed  into  the  cabinet  through  meters,  entering 
the  cabinet  through  a  common  tube.  Thus  they  were  well  mixed 
and  the  rate  of  flow  of  each  was  regulated.  Early  experiments  indi- 
cated that  various  factors  influenced  the  extinction  point,  both  for 
the  oil  and  acetylene  lamp.  Let  me  relate  what  these  factors  were 
and  how  they  exercised  their  influence. 

A.  Actylene  Gas  Pressure. — From  the  outset  it  was  observed 
that  the  pressure  under  which  the  acetylene  gas  was  fed  through 
the  burner  exercised  a  marked  influence  upon  the  extinction  point. 
That  is  to  say,  with  a  series  of  lamps  in  which  the  acetylene  gas 
pressure  varied,  as  indicated  by  the  character  of  the  flame,  it  was 
not  difficult,  in  a  mixture  of  increasing  proportion  of  carbon  dioxide, 
to  foretell  the  order  in  which  the  lamps  would  be  extinguished,  the 
lamps  with  higher  acetylene  pressure  going  out  first.  Indeed,  it 
was  frequently  observed,  where  the  escape  of  gas  from  the  burner 
was  under  such  slight  pressure  as  not  to  give  direction  to  the  flame, 
that  the  extinction  point  would  be  very  much  higher  than  was 
observed  with  the  ordinary  burning  flame.  Care  was  therefore 
exercised  to  make  our  observations  on  lamps  in  which  the  gas 
production  showed  a  normal  amount  of  pressure. 

B.  Air  Movement. — When  there  was  no  movement  of  air,  except- 
ing such  as  resulted  from  the  convection  currents  produced  by  the 
lamps  and  by  the  introduction  of  the  gas  mixture,  the  extinction 
points  were:  for  the  acetylene  lamps,  23  to  25  per  cent,  carbon 
dioxide;  for  the  oil  lamps,  12  to  14  per  cent,  carbon  dioxide.  With 
the  production  of  a  gentle  movement  of  the  air  by  fanning  against 
the  side  of  the  cabinet,  the  extinction  points  were  appreciably 
affected,  being  lowered  in  the  case  of  the  acetylene  lamps  to  22  to  17 
per  cent,  carbon  dioxide ;  in  the  case  of  oil  lamps  to  12  to  10  per  cent, 
carbon  dioxide. 


372  Physiological  Characteristics  of  Acetylene.  { AlAUgS'  mi""" 

With  the  production  of  a  strong  movement  of  the  air,  by  direct 
fanning  of  the  lamps,  in  two  experiments  the  acetylene  lamps  were 
extinguished  when  the  air  contained  9.4  per  cent,  and  9,9  per  cent, 
carbon  dioxide,  respectively,  while  the  oil  lamps  were  extinguished 
by  the  same  breeze  in  atmospheric  air. 

'The  movement  of  the  lamps  worn  on  the  heads  of  the  miners 
would  produce,  in  quiet  air,  the  effects  that  result  from  a  breeze  with 
the  lamps  stationary.  We  may  conclude,  therefore,  that  in  the  case 
of  the  acetylene  lamp  the  extinction  point  is  lower  than  25  per  cent., 
in  proportion  to  the  rapidity  of  motion;  and  with  the  oil  lamps, 
correspondingly  lower  than  14  per  cent. 

C.  Oxygen  Proportion. — In  the  experiments  mentioned,  the  oxy- 
gen was  reduced  only  moderately  by  the  admixture  of  the  carbon 
dioxide  in  the  form  of  pure  gas.  Undoubtedly,  such  reduction  tends 
to  lower  the  carbon  dioxide  extinction  point.  The  effect,  however, 
is  only  moderate,  since  the  oxygen  in  all  experiments  was  distinctly 
more  than  would  sustain  the  flame  if  the  specific  effect  of  the  carbon 
dioxide  were  neglected. 

When  the  admixture  of  carbon  dioxide  is  in  the  form  of  black- 
damp,  however,  the  question  of  the  oxygen  proportion  becomes  an 
important  factor  for  consideration.  In  these  preliminary  investiga- 
tions, we  were  not  able  to  study  the  effect  of  black-damp,  since  with 
the  use  of  so  large  a  cabinet,  the  quantity  of  nitrogen  required  would 
be  much  greater  than  it  was  practical  to  obtain. 

D.  Humidity. — In  a  number  of  experiments,  water  vapor  was 
introduced  into  the  gas  mixture  by  blowing  over  the  surface  of  water 
within  the  cabinet.  In  this  way,  the  humidity  was  raised  from 
approximately  35  to  65  or  80.  Any  effect  upon  flame  extinction  by 
carbon  dioxide  that  may  have  resulted  was  within  the  limits  of  varia- 
tion from  the  other  factors  considered.  The  conclusion  is  therefore 
reached  that  humidity  affects  the  proportion  of  carbon  dioxide 
required  to  produce  flame  extinction  only  within  relatively  narrow 
limits. 

Comparing  now  the  effects  of  carbon  dioxide  increase  on  flame 
extinction  and  respiration,  we  note  that  the  first  effect  is  a  physio- 
logical one,  when  the  proportion  reaches  3  to  4  per  cent.,  there  being 
an  increase  in  the  respiratory  rate  that  is  entirely  adequate  to  warn 
persons  of  the  atmospheric  condition.  Flame  extinction  occurs  with 
oil  at  13  per  cent,  and  acetylene  at  26  per  cent,  in  still  atmosphere, 
but  at  10  per  cent,  and  17  per  cent,  with  moderate  motion.  With 


AnAimiUst'  i9i4im']  Physiological  Characteristics  of  Acetylene.  373 

either  lamp  the  extinction  point  is  too  high  above  the  physiological 
warning  point  to  make  it  of  value  to  the  miner.  The  conditions  will 
have  been  recognized  before  the  extinction  point  is  reached.  Should, 
however,  the  physiological  warning  be  unheeded,  flame  extinction 
will  occur,  first  with  the  oil  and  then  with  the  acetylene  flame,  with 
either  in  ample  time  to  prevent  loss  of  life.  The  margin  of  safety, 
though  greater  with  the  oil  lamp,  is  adequate  with  the  acetylene. 

In  considering  the  influence  of  oxygen  decrease  on  flame  extinc- 
tion, I  shall  make  use  of  observations  made  by  Chester  S.  Heath, 
under  experimental  conditions  different  from  those  I  have  described. 

He  finds  that  with  moderate  motion  an  oil  flame  is  extinguished 
when  the  oxygen  is  reduced  to  16.5  per  cent. ;  in  still  air  to  16.2  per 
cent.  With  acetylene,  at  moderate  motion,  extinction  occurred  at 
12.6  per  cent,  and  was  dimmed  in  still  air  of  the  same  composition, 
being  extinguished  in  still  air  at  1 1.5  per  cent.  It  thus  appears  that 
the  oil  flame  is  extinguished  with  considerably  less  reduction  of 
oxygen  than  the  acetylene,  but  that  the  latter  is  extinguished  before 
the  reduction  is  fatal  to  man,  which  is  at  7  per  cent.  Moreover, 
in  actual  mining  conditions,  where  the  lamp  is  worn  on  the  head,  there 
will  be  sufficient  motion;  hence  extinction  will  occur  at  a  point 
somewhere  above  that  observed  with  the  experimental  conditions. 

Finally,  it  is  not  to  be  forgotten  that  the  condition  of  extreme 
oxygen  reduction  without  carbon  dioxide  increase,  which  was  present 
in  the  experimental  observations,  is  not  encountered  in  actual  mine 
air.  The  specific  action  of  carbon  dioxide  admixture,  that  will  be 
found  in  such  conditions,  will  add  its  effect  to  the  oxygen  decrease 
and  bring  about  the  extinction  of  an  acetylene  flame  at  a  point  which 
is  still  further  removed  from  unphysiological  atmospheric  conditions, 
and  hence  afford  an  increased  margin  of  safety. 

The  miner,  then,  may  conclude  that  a  given  admixture  of  black- 
damp  and  air  in  the  absence  of  other  foreign  gases  will  support 
life:  (1)  if  it  does  not  extinguish  flame;  (2)  if  it  does  not  produce 
markedly  increased  respiration.  Any  atmosphere  which  does  not 
give  these  warnings  is  respirable,  though  not  necessarily  desirable 
for  continuous  respiration.  It  does,  however,  give  warning  either 
physiological,  or  by  the  flame  of  acetylene  as  well  as  oil,  that  is 
adequate  to  prevent  loss  of  life. 


/ 


374  65th  Annual  Session  of  A.  M.  A.     { Am^ul°Zt  ma4rm' 

THE  65TH  ANNUAL  SESSION  OF  THE  AMERICAN 
MEDICAL  ASSOCIATION. 

By  M.  I.  Wilbert,  Washington,  D.  C. 

The  191 3  meeting  of  the  American  Medical  Association  was  held 
in  Atlantic  City,  June  22-26,  and  was  attended  by  3958  members 
who  took  the  time  and  trouble  to  register.  The  registration  this 
year  is  reported  to  have  been  considerably  larger  than  that  of  any  of 
the  previous  sessions  of  the  Association  in  Atlantic  City.  The  work 
of  the  House  of  Delegates  and  its  committees  and  the  proceedings 
of  the  several  sections  of  the  Association  are  reported  at  length  in 
the  Journal  of  the  American  Medical  Association  for  July  4,  1914, 
vol.  63,  pp.  73-130.  The  scientific  papers,  because  of  the  restrictions 
imposed  by  the  House  of  Delegates  at  the  Minneapolis  meeting,  were 
fewer  in  number  than  in  former  years,  but  the  subject  matter  dis- 
cussed was  correspondingly  good,  the  programs  for  the  several 
sections  being  generally  well  carried  out. 

The  Section  on  Pharmacology  and  Therapeutics  had,  as  usual, 
a  program  containing  many  papers  of  pharmaceutical  interest.  Dele- 
gates from  the  American  Pharmaceutical  Association  were  recog- 
nized, and  Prof.  Joseph  P.  Remington,  the  chairman  of  this  dele- 
gation, in  extending  the  felicitations  of  the  organization  he  repre- 
sented, said: 

"  The  American  Pharmaceutical  Association  brings  greetings  to 
the  American  Medical  Association.  It  is  meet  and  proper  that  two 
national  bodies  should  exchange  greetings,  for,  however  they  may 
differ  in  function  and  scope,  they  are  united  in  principle  in  the  one 
great  object  of  promoting  the  health  of  the  nation  in  combating 
disease. 

"  It  is  gratifying  to  know  that  the  Pharmacopoeia  is  practically 
completed,  so  far  as  the  bulk  of  the  work  is  concerned.  The  printing 
of  the  Appendix,  with  the  Tables,  Reagents,  and  Volumetric  Solu- 
tions, will  be  sent  to  the  printer  this  week,  for  this  part  of  the  book 
must  be  printed  first,  in  order  that  members  may  have  it  for  refer- 
ence in  checking  up  the  text  of  the  book. 

"  During  the  past  year  a  number  of  older  remedies  have  been 
deleted  and  new  remedies  admitted.  A  Committee  on  Scope  which 
reports  upon  proposed  admissions  and  deletions  have  finished  their 
work,  but  there  are  still  a  few  questions  which  can  be  settled  after 


AfAuguUst,'  191™'}     65th  Annual  Session  of  A.  M.  A.  375 

the  printing  is  started.  One  of  these  questions  is  the  form  of  so- 
called  bichloride  tablets.  As  is  well  known,  the  enormous  use  of 
these  tablets  is  a  menace  to  the  future  growth  and  prosperity  of  the 
nation.  The  Pharmacopceia  cannot  check  the  use  of  these  tablets, 
but  it  can  at  least  direct  the  form  for  their  use  which  will  prevent  acci- 
dent so  far  as  possible  through  swallowing  the  tablets  or  their  solution. 

"  The  American  Pharmaceutical  Association,  during  the  past 
year,  has  used  its  influence  in  every  possible  way  in  controlling  or 
limiting  the  use  of  habit- forming  drugs  by  national  and  State  legis- 
lation. Committees  have  been  formed  from  the  membership  who 
are  working  to  stamp  out  this  evil. 

"  The  body  which  I  have  the  honor  to  represent  asks  the  assist- 
ance of  your  body  to  aid  in  framing  wise  laws  which  will  make  it 
difficult  for  dopesters  to  continue  their  habits,  and  by  limiting  the 
use  of  these  drugs  to  prescriptions  by  properly  educated  physicians, 
who  are  earnestly  trying  to  curtail  the  evil. 

"  In  educational  matters  Pharmacy  has  progressed  in  the  direc- 
tion of  raising  the  standard  of  education  of  those  entering  Pharmacy, 
and  enlarging  the  curriculum  in  the  colleges.  May  we  not  hope 
that  Medicine  and  Pharmacy  will  be  more  closely  linked  in  the 
future,  and  that  crimination  and  recrimination  will  cease,  or  take 
the  form  of  constructive  criticism,  with  the  intention  of  remedying 
the  evils  and  correcting  abuses,  and  will  be  actuated  by  harmony 
between  the  two  professions." 

Referring  more  particularly  to  the  probable  scope  of  the  U.  S.  P. 
IX,  the  following  table  represents  the  status  of  that  book  at  the 
present  time: 


Number  of  articles  in  text  of  U.  S.  P.  VIII   95$ 

U.  S.  P.  VIII  articles  dismissed  from  U.  S.  P.  IX  list   237 

Number  of  articles  retained  from  U.  S.  P.  VIII  ,   721 

Number  of  new  articles  admitted  to  U.  S.  P.  IX   67 

Total  number  of  articles  in  tentative  list  of  U.  S.  P.  IX   788 


On  motion  of  Dr.  Murray  Gait  Motter,  of  Washington,  D.  C, 
the  Section  on  Pharmacology  and  Therapeutics  of  the  American 
Medical  Association  adopted  the  following  resolution,  which  was 
referred  to  the  House  of  Delegates,  endorsed  by  that  body,  and  thus 
officially  recognized  as  the  opinion  of  the  American  Medical  Associa- 
tion : 


376  65th  Annual  Session  of  A.  M.  A.     {AmxUguD8t"  wm™1" 

"  Whereas,  The  Pharmacopoeia  of  the  United  States  of  America 
should  be,  above  all,  a  book  designed  to  protect  the  public  health 
and  prevent  the  exploitation  of  the  sick  and  afflicted  for  profit ;  now, 
therefore,  be  it 

"Resolved,  That  the  members  of  the  Section  on  Pharmacology 
and  Therapeutics  of  the  American  Medical  Association  request  the 
House  of  Delegates  to  urge  upon  the  Revision  Committee  to  make 
official  in  the  Pharmacopoeia  of  the  United  States  'corrosive  mer- 
curic chloride  pastilles,'  so  that  physicians  may  not  be  compelled 
to  prescribe  this  remedy  under  a  proprietary  name.   Be  it  further 

"Resolved,  That  this  section  endorse  the  form  and  description 
of  corrosive  mercuric  chloride  pastilles  as  described  in  the  German 
Pharmacopoeia,  namely,  of  cylindrical  shape,  twice  as  long  as  thick, 
wrapped  individually  in  paper  bearing  the  name  of  the  medicament, 
'  corrosive  mercuric  chloride  pastilles,'  and  the  word  '  poison  '  in 
suitable  and  striking  letters.    Be  it  further 

"Resolved,  That  a  copy  of  this  resolution  be  forwarded  by  the 
Secretary  of  the  American  Medical  Association  to  the  President 
and  to  each  of  the  officers  of  the  United  States  Pharmacopceial  Con- 
vention, and  also  to  the  Chairman  and  to  each  member  of  the  Com- 
mittee of  Revision  of  the  Pharmacopoeia  of  the  United  States." 

Of  the  many  papers  presented  in  the  Section  on  Pharmacology 
and  Therapeutics,  the  following  contributions  were  of  more  imme- 
diate interest  to  pharmacy : 

Dr.  John  F.  Anderson,  the  chairman  of  the  Section  on  Pharma- 
cology and  Therapeutics,  in  his  address  discussed  some  unhealthy 
tendencies  in  therapeutics  and  referred  more  particularly  to  the  ill- 
advised  use  of  certain  biologic  products,  such  as  the  Friedmann  vac- 
cine for  tuberculosis  and  crotalin  in  the  treatment  of  epilepsy.  In 
summing  up  this  paper  he  suggested  that,  while  advances  in  therapeu- 
tics are  necessary  and  clinical  trials  must  be  made,  these  trials  should 
be  with  adequate  controls  of  otherwise  treated  cases  and  under  cir- 
cumstances in  which  every  stage  can  be  watched  and  the  various  clini- 
cal and  laboratory  observations  be  made  a  matter  of  unbiased  record, 
and  the  best  interests  of  the  patients  thus  safeguarded.  It  is  difficult 
to  secure  these  conditions  outside  of  a  well-equipped  hospital.  Until 
a  new  method  of  treatment  has  received  abundant  confirmation  of  this 
sort  it  is  unjust — to  use  no  stronger  word — to  apply  it  promiscuously 
to  patients  who  are  not  under  constant  observation  and  are  not 
amenable  to  instant  emergency  relief. 


AmAugS;wM!m'}     65th  Annual  Session  of  A.  M.  A.  377 

In  a  paper  on  "  The  Medical  Treatment  of  Chronic  Intestinal 
Stasis,"  W.  A.  Bastedo,  of  New  York,  discussed  the  uses  and  limi- 
tations of  many  of  the  aperients  and  cathartics.  In  commenting  on 
the  now  widely  used  paraffin  oil,  he  called  attention  to  a  series  of  ten 
samples  not  one  of  which  complied  strictly  with  the  requirements 
of  the  Pharmacopoeia,  and  also  stated  that  in  writing  prescriptions  for 
paraffin  oil  or  liquid  petrolatum  it  is  unfortunately  true  that  it  is  prac- 
tically necessary  to  specify  some  established  brand,  as  the  material 
supplied  in  retail  drug  stores  very  seldom,  if  ever,  complies  with  the 
requirements  of  the  Pharmacopoeia  or  is  of  an  otherwise  satisfactory 
nature. 

In  a  paper  on  active  immunization  in  diphtheria  by  toxin-anti- 
toxin mixtures,  William  H.  Park,  of  New  York,  reported  on  recent 
progress  in  the  prophylaxis  of  diphtheria  and  reviewed  the  present- 
day  knowledge  regarding  immunization  and  the  possible  recognition 
of  immunization  by  skin  reaction. 

In  a  paper  on  the  use  of  diphtheria  antitoxin  in  the  treatment  of 
diphtheria,  Samuel  S.  Woody,  of  Philadelphia,  recommended  the 
administration  of  much  larger  doses  than  are  used  at  present,  and  also 
asserted  that  the  number  of  antitoxin  units  to  be  administered  should 
be  in  keeping  with  the  stage  of  the  disease.  He  also  stated  that  as  a 
prophylactic  diphtheria  antitoxin  was  uncertain  and  in  a  great  meas- 
ure unsatisfactory  in  its  results,  and  that  to  be  efficacious  in  the  treat- 
ment of  diphtheria,  antitoxin  must  be  given  at  the  earliest  possible, 
moment  and  in  large  doses. 

In  addition  to  the  resolution  endorsing  the  inclusion  of  pastilles 
of  corrosive  mercuric  chloride  in  the  Pharmacopoeia  of  the  United 
States,  the  House  of  Delegates  also  adopted  the  following  recom- 
mendation of  pharmaceutical  interest  suggested  by  the  Council  on 
Medical  Education  and  endorsed  by  the  reference  committee: 

"  Your  committee  also  recommends  that  the  Council  be  instructed 
to  urge  all  medical  colleges  to  adopt  the  nomenclature  of  thte  Pharma- 
copoeia of  1910,  and  to  use  the  metric  system  in  their  teaching." 

The  scientific  exhibit  was  of  unusual  interest,  and  the  work  dis- 
played was  not  alone  excellent,  but  much  of  it  was  of  immediate  prac- 
tical value  to  the  profession.  The  commercial  exhibit  attracted  con- 
siderable attention  and  was  unusually  free  from  objectionable 
features  in  the  way  of  proprietary  and  semi-proprietary  prepara- 
tions not  recognized  by  the  Council  on  Pharmacy  and  Chemistry. 

The  officials  for  the  Section  on  Pharmacology  and  Therapeutics 


378 


Book  Reviews. 


J  Am.  Jour.  Pharm. 
t     August,  1914. 


for  the  coming  year  are :  Chairman,  R.  A.  Hatcher ;  vice-chairman, 
J.  Ray  Arneil ;  secretary,  M'.  I.  Wilbert ;  delegate,  John  F.  Anderson, 
and  alternate,  Ray  L.  Wilbur. 

At  the  opening  meeting  of  the  Association  on  Tuesday  morning 
Dr.  Victor  C.  Vaughan,  of  Ann  Arbor,  Mich.,  was  installed  as  presi- 
dent, and  at  the  concluding  session  of  the  House  of  Delegates  on 
Thursday  afternoon  Dr.  Wm.  L.  Rodman,  of  Philadelphia,  was 
selected  as  the  president-elect  and  San  Francisco  chosen  as  the  place 
of  meeting  for  1915. 


BOOK  REVIEWS. 

Digest  of  Comments  on  the  Pharmacopoeia  of  the  United 
States  of  America  and  on  the  National  Formulary  for  the 
Year  Ending  December  31,  1912.  By  M.  I.  Wilbert  and  M.  G. 
Motter. 

One  hardly  realizes  the  vast  amount  of  writing  done  annually  in 
reference  to  pharmacopceial  matters  until  one  peruses  the  above 
useful  compilation  and  the  several  that  preceded  it. 

We  do  not  say  that  Charles  Rice  "  builded  better  than  he  knew," 
because  he  knew  many  things,  if  all  we  have  learned  of  him  is 
true,  but  he  certainly  built  wisely  and  with  the  foresight  possessed 
by  a  great  mind  when  he  suggested  and  carried  out  the  idea  of  com- 
pilation and  classification  of  critical  references  anent  matters  pharma- 
ceutical. That  we  live  in  a  day  and  under  a  form  of  government  that 
sees  its  way  clear  to  carry  this  idea  to  fuller  fruition  augurs  well  for 
pharmacy  in  this  country.  Jofin  K.  Thum. 

Annual  Report  of  the  Investigations  Carried  Out  under 
the  Supervision  of  the  Therapeutic  Research  Committee  of 
the  Council  on  Pharmacy  and  Chemistry  of  the  American 
Medical  Association,  Volume  II,  1913. 

This  small  volume  of  11 1  pages  embodies  the  results  of  some 
practical  research  work  that  is  bound  to  have  an  influence  for  good 
on  medicine  and  pharmacy.  Both  physicians  and  pharmacists  would 
do  well  to  purchase  this  little  volume,  which  can  be  obtained  for 
a  small  sum,  for  it  will  put  them  in  possession  of  some  positive  knowl- 
edge on  the  possibilities  and  limitations  of  some  well-known  drugs. 
While  it  may  be  true,  as  is  sometimes  said,  that  medicine  is  not  an 


AmAuKuUJ;  wum  }     Philadelphia  College  of  Pharmacy.  379 

"  exact  science,"  yet  if  it  is  ever  to  be  raised  from  the  slough  of 
empiricism,  work  of  this  kind  must  be  done  and  persistently  promul- 
gated among  the  members  of  the  professions. 

John  K.  Thum. 


PHILADELPHIA  COLLEGE  OF  PHARMACY. 

Quarterly  Meeting. 

The  quarterly  meeting  of  the  Philadelphia  College  of  Pharmacy 
was  held  June  29,  1914,  at  4  p.m.,  in  the  Library;  the  President, 
Howard  B.  French,  in  the  chair.  •  Fifteen  members  were  present. 
The  minutes  of  the  annual  meeting,  held  March  30,  1914,  were  read 
and  approved. 

The  minutes  of  the  Board  of  Trustees  for  March,  April,  and 
May  were  read  by  the  Registrar,  J.  S.  Beetem,  and  approved.  The 
report  of  the  Committee  on  Necrology  was  read  by  the  Chairman, 
and  referred  for  publication  in  the  American  Journal  of 
Pharmacy. 

Professor  Stroup  reported  verbally  for  the  delegates  to  the  Penn- 
sylvania Pharmaceutical  Association.  The  attendance  was  some- 
what smaller  than  usual.  The  reception  of  delegates  from  other 
organizations  and  reports  of  delegates  to  other  bodies  were  the 
features  of  the  first  day's  session.  A  large  number  of  papers  were, 
as  usual,  presented,  the  one  on  "  Bacterial  Vaccines  and  Serums,''  by 
Dr.  A.  P.  Hitchens,  being  most  interesting.  The  report  of  the 
Legislative  Committee  and  the  report  of  the  Secretary  of  the  State 
Pharmaceutical  Board  were  also  presented.  The  president,  R.  H. 
Lackey,  made  a  number  of  recommendations  which,  after  being  re- 
ferred to  a  special  committee,  were  adopted.  The  Association  elected 
the  former  secretary,  E.  F.  FlefYner,  president,  and  David  J.  Reese, 
secretary.  The  next  meeting  is  to  be  held  at  Forest  Park,  Pike 
County. 

The  delegates  to  the  Delaware  Pharmaceutical  Association  re- 
ported verbally  by  its  chairman,  Dr.  A.  W.  Miller.  The  meeting 
was  held  at  Hotel  Du  Pont,  Wilmington,  on  June  4th.  The  reports 
of  the  officers  and  committees  occupied  the  morning  session.  The 
meeting  was  not  a  very  large  one,  but  a  very  harmonious  one.  Your 
delegate  was  accorded  a  cordial  welcome,  who  urged  upon  the 
members  their  help  to  influence  congressional  action  in  securing  a 


380  Philadelphia  College  of  Pharmacy.  {k\*^*imA^* 

site  for  the  statue  to  Professor  Procter  in  front  of  the  Smithsonian 
Institution. 

The  delegates  to  the  New  Jersey  Pharmaceutical  Association  re- 
ported through  the  chairman,  George  M.  Beringer.  The  44th  annual 
meeting  was  held  at  Hotel  Breslin,  Lake  Hopatcong,  June  16th  to 
19th.  The  absence  of  other  members  of  the  delegation,  owing  to  the 
commencement  exercises  of  the  College  occurring  at  the  same  time, 
was  very  much  regretted.  The  meeting  was  one  of  the  largest 
attended  and  most  interesting  sessions  ever  held.  The  sessions  were 
well  attended,  and  under  the  able  executive  the  business  was  thor- 
oughly yet  expeditiously  considered.  Legislative  matters  were  again 
one  of  the  principal  topics  considered  and  the  incoming  Legislative 
Committee  was  instructed  to  have  the  proposed  new  pharmacy 
law,  with  a  prerequisite  clause,  again  presented  to  the  next 
Legislature,  and  to  use  their  best  endeavors  to  have  this  bill 
enacted.  The  Committee  on  Papers  and  Queries  presented  an 
unusually  interesting  report.  About  twenty  papers  were  read  and 
discussed.  A  number  of  these  were  contributions  from  the  members 
of  this  College.  The  subjects  covered  a  wide  range:  commercial, 
educational,  legal,  scientific,  and  practical  pharmaceutical  questions 
were  treated  in  these  papers.  Of  no  less  interest  were  the  discus- 
sions they  provoked.  The  internal  alfairs  and  finances  of  the  Asso- 
ciation were  subjects  for  earnest  consideration.  The  President,  in 
his  annual  address,  advocated  an  increase  in  the  dues  in  order  to 
avoid  a  deficiency.  Mr.  John  C.  Gallagher,  of  Jersey  City,  was 
elected  president,  and  Mr.  G.  M.  Hays  Deemer,  of  Atlantic  City, 
was  elected  vice-president.  The  entertainments  provided  by  the 
Local  Committee  and  Travelling  Men's  Auxiliary  were  good  and 
sufficient  for  the  occasion  without  infracting  upon  the  time  needed 
for  business. 

Professor  Kraemer  presented  the  following  resolution  referring 
to  a  celebration  of  the  fiftieth  anniversary  of  the  founding  of  the 
Alumni  Association : 

"As  the  session  of  1914-15  will  mark  fifty  years  since  the 
Alumni  Association  of  the  Philadelphia  College  of  Pharmacy  was 
established,  and  as  the  founders  rendered  yeoman  service  in  the 
development  of  the  educational  facilities  of  the  College,  Resolved, 
That  the  College  recognize  this  interest  in  her  former  students 
and  arrange  for  a  fitting  celebration  to  commemorate  this  mile- 
stone in  the  history  of  the  Association." 

The  reading  of  the  paper  caused  considerable  discussion.  Mr. 


AlAiigu"t'  SiT"')    Philadelphia  College  of  Pharmacy. 


38i 


French  said  that  the  Alumni  Association  had  been  foremost  in  all 
the  advances  the  College  had  made,  either  as  the  originator  or  sup- 
porter of  these  advanced  movements.  The  discussion  was  further 
participated  in  by  Messrs.  Beringer,  Kraemer,  Foley,  French,  Miller, 
and  Stroup,  when  Mr.  Beringer  moved  that  a  joint  committee  of  the 
Board  of  Trustees  and  the  Alumni  Association  be  appointed  to 
consider  the  matter.  Adopted. 

Professor  Kraemer  presented  a  framed  receipt  for  two  hundred 
dollars,  contributed  by  the  Class  of  1889  for  the  Centenary  Fund  now 
in  process  of  collection.  On  motion,  it  was  voted  to  place  it  in  the 
Library. 

Professor  Kraemer  referred  to  the  work  which  had  been  done 
during  the  past  fifteen  years,  prior  to  the  establishment  of  the  present 
course  in  Bacteriology,  and  requested  that  a  succinct  account  of  the 
work  be  compiled  from  the  reports  of  the  Committees  on  Instruction 
and  Examination. 

Mr.  Beringer,  in  commenting  on  the  paper  just  read,  said  he 
wanted  to  call  particular  attention  to  the  advances  the  College  has 
made  in  its  courses  of  instruction.  There  should  be  still  further 
advances  made.  We  should  have  post-graduate  courses.  No  other 
college  is  giving  the  advanced  courses  that  we  are  giving,  especially 
in  Pharmacognosy.  More  publicity  should  be  given  to  the  instruc- 
tion given  in  the  College.  Our  third-year  class  should  be  augmented 
from  graduates  of  other  institutions  who  are  receiving  less  than  we 
are  giving. 

The  President  made  the  following  appointments : 

Committee  on  Nominations:  W.  A.  Rumsey,  E.  F.  Cook,  W.  L. 

Cliffe,  Otto  Kraus,  John  K.  Thum. 

Committee  on  Necrology :  Henry  Kraemer,  Joseph  W.  England, 

C.  A.  Weidemann. 

C.  A.  Weidemann,  M.D., 

Recording  Secretary. 


ABSTRACTS  FROM  MINUTES  OF  THE  BOARD  OF 
TRUSTEES. 

March  3,  1914- — Thirteen  members  present. 
Committee  on  Property  reported  that  a  lunch  room  had  been 
opened,  that  the  lunches  furnished  were  of  good  quality,  and  that 


382  Philadelphia  College  of  Pharmacy.  \A\^i,vdu.m' 

the  number  of  student  patrons  was  greater  than  had  been  expected. 
The  caterer  expressed  his  satisfaction  at  the  results  of  the  undertak- 
ing, and  it  was  regarded  a  success.  The  committee  suggested  the 
advisability  of  larger  accommodations  for  the  next  session.  The 
committee  also  reported  complaints  having  been  made  concerning 
students  smoking  throughout  the  building,  and  advocated  the  en- 
forcement of  more  stringent  rules  governing  this  practice,  confining 
smoking  to  the  cemented  portions  of  the  first  floor  and  basement. 

Committee  on  Library  reported  398  books  accessioned  during  the 
month,  making  a  total  of  6676  books  ready  for  cataloging.  Two 
hundred  and  forty-one  persons  had  used  the  Library. 

Committee  on  Examinations  presented  the  results  of  the  recent 
examinations  held  at  the  end  of  the  first  semester  for  the  classes 
of  the  first,  second,  and  third  years. 

Committee  on  By-laws  proposed  several  amendments :  To  amend 
Article  8,  Section  3.  To  amend  Article  11,  making  same  Article  12, 
and  to  introduce  a  new  Article  on  Scholarships  and  Fellowships,  as 
Article  11.    Action  was  deferred  until  the  next  meeting. 

Committee  on  Athletics  presented  a  communication  from  the  stu- 
dents representing  the  track  team.  The  committee  felt  that  the  mat- 
ter of  athletics  was  one  to  be  assumed  by  the  Alumni  Association  and 
to  be  under  their  control  and  support.  The  subject  was  referred  to 
the  President  of  the  Alumni  Association. 

Committee  on  Membership  reported  favorably  on  the  application 
of  Miss  Agnes  Duvoisin ;  a  ballot  was  taken  and  she  was  unani- 
mously elected  to  active  membership. 

April  7,  1914. — Thirteen  members  present.  A  communication 
was  received  from  the  Recording  Secretary  of  the  College,  announc- 
ing the  election  of  officers  for  the  ensuing  year  and  three  Trustees  for 
three  years  (see  this  Journal,  p.  229). 

Nominations  for  officers  of  the  Board  being  in  order,  George  M'. 
Beringer  was  elected  chairman ;  Walter  A.  Rumsey,  vice-chairman, 
and  Jacob  S.  Beetem,  registrar. 

The  Chairman  read  a  communication  from  the  stafY  of  the 
"  Graduate  "  1913,  offering  to  present  a  loving  cup  to  be  awarded 
to  the  first-year  class  1914,  and  competed  for  thereafter  under  the 
rules  governing  the  award  of  the  President's  Cup.  On  motion  the 
offer  was  accepted  and  the  appreciation  of  the  Board  expressed. 

Dr.  A.  W.  Miller  read  a  communication  from  Professor  Ernest 
Gilg  acknowledging  receipt  of  his  Certificate  of  Honorary  Member- 


ADAuJg0.rst;  1914™' }     Philadelphia  College  of  Pharmacy. 


383 


ship,  for  which  he  expressed  appreciation  and  offered  the  College  a 
set  of  his  books.  The  offer  was  accepted  with  the  thanks  of  the 
Board. 

The  Chairman  announced  the  Standing  Committees  for  the  ensu- 
ing year,  as  follows :  Property,  Howard  B.  French,  chairman ; 
Library,  Samuel  P.  Sadtler,  chairman ;  Museum  and  Herbarium, 
O.  W.  Osterlund,  chairman ;  Finance,  Howard  B.  French,  chairman ; 
Supplies,  H,  K.  Mulford,  chairman;  Accounts  and  Audits,  C.  A. 
Weidemann,  chairman;  Instruction,  George  M.  Beringer,  chairman; 
Scholarships,  Joseph  P.  Remington,  chairman;  Examinations, 
William  L.  Cliff  e,  chairman  ;  Theses,  Joseph  W.  England,  chairman ; 
Discipline,  Howard  B.  French,  chairman;  Announcement,  Samuel 
P.  Sadtler,  chairman ;  Commencement,  Walter  A.  Rumsey,  chairman ; 
Alumni,  Joseph  W.  England,  chairman;  Appropriations,  composed  of 
chairmen  of  all  committees  empowered  to  make  expenditures,  also 
the  chairman  of  the  Board  of  Trustees,  the  chairman  of  the  Com- 
mittee on  Finance,  and  the  Treasurer. 

Mr.  French  presented  souvenirs,  consisting  of  invitations,  pro- 
grams, menus,  advertisements,  etc.,  relating  to  past  affairs  of  the 
College.  These  were  of  historic  interest  and  were  referred  to  the 
Historical  Committee. 

Professor  Remington  referred  to  the  Panama  Exhibition  in  191 5, 
expressing  the  thought  that  it  would  be  to  the  advantage  of  the 
College  to  exhibit  a  line  of  official  and  N.  F.  preparations,  together 
with  historical  matter,  and  suggested  that  a  committee  be  appointed 
to  make  arrangements  and  that  the  College  make  an  early  appli- 
cation for  space.  On  motion  it  was  voted  that  a  committee  of  five 
be  appointed. 

April  21,  1914. — Eleven  members  were  present. 

Committee  on  Examinations  reported  favorably  on  the  appli- 
cation of  Prof.  Edwin  Leigh  Newcomb,  P.D.,  for  the  degree  of 
Master  in  Pharmacy  in  course,  all  the  requirements  having  been 
complied  with.  A  ballot  was  ordered  and  the  applicant  was  unani- 
mously elected  to  receive  the  degree  at  the  next  commencement. 

Committee  on  Instruction  reported  that  they  had  held  a  number 
of  meetings  to  consider  the  annual  reports  from  the  Faculty.  Ab- 
stracts from  these  reports  are  as  follows : 

Department  of  Pharmacy:  The  record  of  attendance  as  now  made 
obligatory  has  been  of  special  value.  The  extra  lectures  on  pharma- 
ceutical subjects  have  been  attended  by  a  much  larger  number  of 


384  Philadelphia  College  of  Pharmacy.     {^^S*  Su"0' 

students  than  heretofore ;  the  increased  time  given  to  this  department 
has  permitted  considerable  additional  instruction  in  Operative 
Pharmacy.  It  is  thought  desirable  that  this  department  be  fur- 
nished with  a  lantern  for  illustrating  lectures  on  prescriptions,  etc. 
Numerous  slides  have  been  accumulated,  and  these  are  used  to 
advantage,  but  they  are  not  as  effective  as  the  projection  of  the 
actual  prescription. 

The  course  in  Commercial  Training  has  been  greatly  increased, 
and  the  former  indifference  of  the  students  has  given  way  to  eager- 
ness to  absorb  information. 

The  instructor  in  Latin  reports  that  his  work  has  been  satisfactory. 

Department  of  Chemistry:  Professor  Sadtler  reports  upon  the 
work  of  the  second-  and  third-year  classes.  By  the  lengthening  of 
the  College  year,  and  the  increase  in  the  hours  of  instruction,  a  more 
extended  course  of  instruction  is  given.  In  addition  to  the  course 
of  public  lectures  that  have  been  given  in  recent  years  to  the  third- 
year  classes,  it  is  thought  that  a  series  of  lectures  for  the  second- 
year  class  could  be  introduced  to  considerable  advantage.  As  the 
instruction  to  the  second-year  class  covers  many  of  the  commercial 
chemicals,  it  would  seem  that  a  series  of  lectures  bearing  upon  that 
subject  would  be  especially  beneficial. 

Department  of  Materia  Medica:  Increased  attention  has  been 
given  to  the  physiological  assaying  of  drugs  with  good  results. 

Department  of  Botany  and  Pharmacognosy :  Advanced  methods 
have  been  used.  With  each  laboratory  lesson  a  mimeographed  outline 
of  the  work  is  given  the  students,  printed  on  sheets  of  uniform  size 
to  fit  in  the  notebooks  used  in  this  department.  In  the  first  year  the 
initiative  work  is  on  the  principal  groups  of  plants,  which  is  a  little 
difficult  for  the  beginner,  and  interest  has  been  stimulated  by  periods 
of  debates.  A  Biological  Club  has  been  organized;  a  program  is 
arranged,  and  the  discussions  are  illustrated  with  the  lantern.  In 
the  second  year  the  subject  matter  has  been  presented  in  groups 
according  to  their  natural  relationships.  Two  hundred  and  fifty-four 
types  of  drugs  have  been  arranged  in  twelve-ounce  jars,  which  have 
been  consulted  at  recess  and  other  times ;  the  reviews  have  been  of 
great  help  also.  The  third-year  work  has  been  in  the  study  of  choco- 
late products,  spices,  and  a  number  of  National  Formulary  drugs. 
Professor  Kraemer,  having  been  relieved  of  the  teaching  in  Bacteri- 
ology, has  been  enabled  to  develop  a  special  course  in  Microscopy 


^./gust;i9ura'}     Philadelphia  College  of  Pharmacy.  385 

for  the  Special  Chemical  students.  It  is  suggested  that  time  be 
provided  for  compulsory  botanical  excursions  to  be  considered  as 
part  of  the  laboratory  exercises.  The  green-house  and  roof  garden 
continue  to  be  very  serviceable  in  giving  instruction. 

Department  of  Analytical  Chemistry:  The  instruction  in  this 
department  has  been  carried  on  in  accordance  with  the  published 
announcement  and  outlined  course.  The  results  have  been  very 
satisfactory,  and  a  continuance  along  the  same  lines  is  recommended. 

Department  of  Bacteriology:  The  attendance  at  lectures  was  uni- 
formly good.  The  laboratory  instruction  in  the  regular  course  will 
be  doubled. 

Department  of  Physical  Culture:  About  two-thirds  of  the  class 
presented  themselves  for  examination.  New  record  cards  have  been 
prepared.  Many  of  the  students  were  found  to  be  under  weight  and 
Hat-chested,  and  the  proper  gymnastic  training  for  these  conditions 
was  given. 

Physical  Director:  This  report  contains  a  number  of  interesting 
items  on  the  work  of  the  department. 

May  5,  1914. — Eighteen  members  present. 

Committee  on  Library  reported  472  books  shelf -listed,  making 
a  total  of  7690  books  ready  to  be  catalogued.  Use  of  Library  for 
the  month  by  382  persons. 

Committee  on  Supplies  were  given  power  to  act  in  procuring 
additional  microscopes. 

Committee  on  Examinations  reported  having  received  a  com- 
munication from  the  Secretary  of  the  State  Pharmaceutical  Exam- 
ining Board,  requesting  that  the  final  result  of  the  third-year  exam- 
inations be  recorded  in  time  to  comply  with  the  State  Board  require- 
ments. 

President  Howard  B.  French  presented  to  the  College,  on  behalf 
of  Mrs.  Mary  I.  Banks,  a  check  for  $5000  with  which  to  establish 
a  fellowship  in  memory  of  her  father,  the  late  Clayton  French. 
The  following  resolution  was  adopted : 

Resolved,  That  the  Board  of  Trustees  of  the  Philadel- 
phia College  of  Pharmacy  gratefully  acknowledge 
receipt  of  Five  Thousand  Dollars  through  the 
hands  of  Mr.  Howard  B.  French  from  Mrs.  Mary 
I.  Banks,  to  be  used  in  establishing  a  fellowship 
in  honor  of  her  father,  the  late  Clayton  French. 


386 


Osage  Orange  as  Commercial  Dyestuff.  {Am±*™*t'  SS™' 


Resolved,  That  a  tablet  be  erected  in  the  hallway  of 
the  College  bearing-  the  following  inscription : 

1824  1890 

Clayton  French 

FELLOWSHIP 
Established  by  his  daughter 

Mary  I.  Banks 

May  16th,  1914 

The  Dean  moved  that  the  gift  be  accepted  and  that  the  grateful 
thanks  of  the  College  be  expressed.  It  was  further  resolved  that 
the  income  from  the  fund  should  be  used  for  advanced  research  work. 

Mr.  Campbell  referred  to  the  N.  A.  R.  D.  Convention  to  be  held 
in  August  in  this  city,  and  favored  representation  by  the  College. 
After  discussion,  a  committee  of  five,  consisting  of  Messrs.  Campbell, 
Osterlund,  Remington,  Mulford,  and  Evans,  was  appointed  to  con- 
sider the  matter  and  report  to  the  Board. 

The  Chairman  announced  the  appointment  of  the  Special  Com- 
mittee on  Panama  Exposition :  Joseph  P.  Remington,  chairman ; 
Joseph  W.  England,  Warren  H.  Poley,  H.  K.  'Mulford,  C.  Stanley 
French;  associates,  Professors  E.  F.  Cook,  F.  X.  Moerk,  Henry 
Kraemer.    With  authority  to  add  to  their  number. 


OSAGE  ORANGE,  ITS  VALUE  AS  A  COMMERCIAL 
DYESTUFF. 

It  has  long  been  known  in  the  Southwest  that  the  wood  of  the 
Osage  orange  tree  contains  a  dyestuff  that  would  give  a  more  or 
less  fast  yellow  color.  An  examination  of  the  wood  from  Texas  by 
F.  W.  Kressmann  showed  that  it  not  only  contains  moric  acid  and 
morintannic  acid,  the  same  as  fustic  wood,  but  also  that  the  dyeing 
principles  are  present  in  amount  to  be  commercially  valuable.  A 
comparative  series  of  dyeing  experiments  made  with  fustic  and 
Osage  orange  wood  and  extracts  showed  the  latter  to  be  of  equal 
value  with  fustic  in  regard  to  depth  of  colors  produced,  the 
amount  of  extract,  the  character  of  the  dyeing,  and  fastness  to 
light,  weather,  washing,  etc. — Science,  vol.  xl,  July  3,  1914,  p.  37. 


THE  AMEEIOAN 


JO 


Rrog^NUS  p^j%hiAna:  its  history,  growth, 

METj$$$JS  OF  CpLI/ECTION  AND  BIBLIOGRAPHY. 


AL  OF  PHARMACY 


^QfiPTEMBER,  1 91 4 


Johnson  and  Edith  Hindman. 


Rhamnus  Purshiana  was  discovered  in  Montana,  on  the  banks 
of  a  tributary  of  the  Columbia  River,  in  1805  or  1806,  by  the  mem- 
bers of  the  first  North  American  transcontinental  exploring  expe- 
dition under  the  command  of  Lewis  and  Clark  ("  Silva  of  North 
America,"  by  Sargent,  vol.  2,  1895,  pp.  37-40).  It  was  also  found 
by  Lewis  and  Clark  in  what  is  now  known  as  Oregon  and  Washington. 
On  their  return  journey  they  took  with  them  a  specimen  of  the 
shrub  for  identification.  The  exact  place  where  Lewis  and  Clark 
collected  the  type,  later  examined  by  Pursh,  was  Camp  Chopunish, 
situated  on  the  east  bank  of  the  Kooskooskee  (Clearwater)  River, 
about  two  miles  below  what  is  now  known  as  Kamiah,  Idaho  (Con- 
tributions from  the  National  Herbarium,  vol.  11,  "Flora  of  Wash- 
ington," by  Piper). 

This  plant,  along  with  a  number  of  other  unknown  botanical 
specimens  collected  on  the  journey,  was  given  to  Frederick  Pursh, 
a  German  botanist,  of  Philadelphia,  for  botanical  study.  Frederick 
Pursh  lived  in  America  between  the  years  1799  and  1812.  In  1812 
he  went  to  London,  where,  in  1814,  he  published  a  description  of 
the  plant,  giving  it  the  name  of  Rhamnus  alnifolia  ("  Flora  America? 
Septentrionalis,"  vol.  1,  1814,  p.  166). 

Augustin  Pyramus  de  Candolle  (1 778-1841)  found  that  another 
plant  had  been  named  Rhamnus  alnifolia  by  C.  L.  de  Brutelle 
L'Heritier  in  1775.  In  1825  he  changed  the  name  of  the  plant  de- 
scribed and  named  by  Pursh  as  Rhamnus  alnifolia*  to  Rhamnus 
Purshiana,  in  honor  of  Pursh  (de  Candolle,  "Prodromus  Systematis 
Naturalis,"  vol.  2,  1825,  p.  25). 

The  following  is  a  translation  of  the  Latin  description  of  Rhamnus 


(387) 


388 


Rhamnus  Purshiana. 


f  Am.  Jour.  Pharm. 
(  September,  1914. 


alnifolia  by  L'Heritier,  Rhamnus  alnifolia  by  Pursh,  and  Rhamnus 
Purshiana  by  de  Candolle,  as  copied  in  Latin  by  John  Uri  Lloyd  from 
the  original  works  in  the  Lloyd  Library,  Cincinnati,  Ohio  • 

Rhamnus  alnifolius  (L'Heritier,  "  Sertulum,"  p.  5),  erect;  leaves 
oval,  serrulate,  veins  straight,  pointed  obliquely  toward  the  end,  under 
surface  smooth,  with  flowers  dioecious ;  peduncle  one  flowered,  with 
calyx  acute,  fruit  top  shaped. 

Rhamnus  alnifolius  (Pursh),  R.  inermis  (unarmed  or  without 
thorns)  ;  leaves  oval,  denticulate,  short  acuminate;  base  cordate  and 
slightly  curved,  veins  underneath  covered  with  hairs;  peduncle  split 
twice  into  two  parts,  berry  globose  but  depressed.  On  the  banks  of 
the  river  Kooskooskee.  Berries  purple,  very  highly  esteemed  by  the 
Indians  of  that  country.  (Pursh  s  "  Flora  American  Septentrionalis," 
vol.  1,  1814,  p.  166.) 

Rhamnus  Purshianus  (de  Candolle  J,  erect;  leaves  oval,  denticu- 
late, short  acuminate,  cordate  and  slightly  curved,  veins  underneath 
covered  with  hairs,  peduncle  split  twice  into  two  parts,  berry  globose 
but  depressed.  On  the  banks  of  the  river  Kooskooskee.  Rhamnus 
alnifolius  (Pursh,  "Flora,"  vol.  1,  p.  166,  not  L'Heritier)  ("  Pro- 
dromits  Systematis  Naturalis  Regni  Vegetabilis,"  by  de  Candolle, 
vol.  2,  1825,  p.  25). 

Johann  Friedrich  (Iwan  Iwanowitsch)  Eschscholtz,  a  Russian 
naturalist,  discovered  the  plant  on  the  shores  of  San  Francisco  Bay, 
California,  in  1816,  and  it  was  described  by  him  in  the  "  Memoirs  of 
the  Academy  of  St.  Petersburg,"  vol.  10,  .1826. 

Prof.  C.  S.  Sargent  ("  Notes  on  North  America  Trees,"  vol.  23; 
Garden  and  Forest,  Feb.  18,  p.  75;  The  Pacific  Druggist,  April  15, 
1891)  states  that  in  1838  Rafinesque  describes  in  the  "  Silva  Tellu- 
riana  "  his  Personon  Laurifolium,  his  description  being  drawn  from 
a  plant  which  he  found  in  Bartram's  Botanic  Gardens,  in  Philadel- 
phia. It  is  a  tree,  he  says,  from  the  Oregon  mountains  with  elliptical, 
acute,  sub-entire,  shining,  glabrous  leaves  pubescent  on  the  lower 
surface  when  young,  reniform  petals,  and  slight  emarginate 
stigma.  The  plant  in  Bartram's  Gardens  was  twenty  feet  high, 
and  the  berries  formed  fine  clusters  and  assumed  three  colors,  being 
by  turn  green,  red,  and  black  when  fully  ripe.  This  is  the  earliest 
record  of  the  cultivation  of  Rhamnus  Purshiana,  for  there  does  not 
seem  to  be  much  doubt  that  it  was  this  plant  that  Rafinesque  had  in 
mind.  Certainly  there  is  no  other  tree  from  the  mountains  of 
Oregon  which  could  be  made  to  answer  to  this  description.   If  Lewis 


Am.  Jour.  Fharm.  ) 
September,  1914.  / 


Rhamnus  Purshiana. 


389 


and  Clark,  as  is  possible  in  the  case  of  the  plant  o^  whose  medicinal 
value  they  must  have  learned  from  the  Indians,  had  brought  home 
seed,  these  might  very  well  have  produced  by  1838  trees  twenty  feet 
in  height. 


Fig.  i.— A  Cascara  tree  on  University  of  Washington  campus. 


Rhamnus  Purshiana  is  claimed  to  have  been  known  since  the 
early  part  of  the  nineteenth  century  to  the  Mexicans  and  Spanish 
priests  of  Old  California.    Tt  was  known  by  the  Spanish  name  of 


39Q 


Rhamnus  Purshiana. 


\  Am.  Jour.  Pharm. 
(   September,  1914. 


Cascara  Sagrada^  (sacred  bark),  so  named  because  the  wood  was 
supposed  to  be  identical  with  the  "Shittim  "  or  "  Chittim  "  wood 
used  in  the  building  of  the  Ark  of  the  Covenant. 

Common  Names. — In  the  different  localities  where  it  grew  the 
tree  was  known  by  the  Indians  and  early  white  settlers  by  the  follow- 
ing names :  Bearberry,  Barberry,  Coffee-berry,  Coffee-tree,  Bitter- 
bark,  Bear-wood,  Wahoo,  Shittim-wood,  Chittim-wood,  and  Cas- 
cara Sagrada. 

Range. — Rhamnus  Purshiana  is  widely  distributed  throughout 
the  Northwest.  It  is  found  in  small  quantities  at  the  head  of  the 
Portland  canal  and  mouth  of  the  Cnuk  River  in  Southeastern  Alaska 
and  in  northern  British  Columbia,  in  commercial  quantities  on  the 
west  slope  of  the  Cascade  Mountains  of  southern  British  Columbia, 
Washington,  Oregon,  and  northern  California. 

It  grows  in  the  Mission  Mountains  and  near  the  Flat-head  Lake 
in  Montana,  in  the  Bitter-root  Mountains  and  Seven-Devil  Moun- 
tains in  Idaho.  It  occurs  occasionally  on  the  eastern  slope  of  the 
Sierra  Nevada  Mountains,  and  then  reappears  in  the  mountains  of 
Colorado  and  western  Texas.  In  one  of  its  forms  it  is  scattered 
throughout  the  mountainous  regions  of  southern  California,  Arizona, 
New  Mexico,  and  northern  Mexico. 

Commercial  Range. — The  tree  grows  abundantly  and  attains 
its  greatest  size  on  the  western  slope  of  the  Cascade  range  of  moun- 
tains in  Washington,  Oregon,  northern  California,  and  southern 
British  Columbia.  Plenty  of  moisture  and  a  slightly  sandy  soil  are 
favorable  factors  for  its  rapid  development. 

It  is  usually  found  in  small  river  bottoms,  sides  and  bottoms  of 
canyons,  growing  under  the  shelter  of  coniferous  forests,  around  the 
edges  of  swamps,  and  on  slightly  elevated  moist  areas. 

With  favorable  soil  and  moisture  the  tree  frequently  springs  up 
in  places  formerly  covered  with  coniferous  trees  that  have  been 
destroyed  by  fire.  It  is  seldom  found  in  broad  river  bottoms  or 
valleys  on  account  of  being  crowded  out  by  the  more  thrifty  and  rapid- 
growing  alder  and  cottonwood  trees. 

The  tree  is  found  at  sea  level  and  up  to  an  altitude  of  1800  to 
2000  feet.  Men  working  in  the  cascara  forests  of  Washington  state 
that  the  tree  grows  to  a  height  of  twenty  to  thirty  feet  and  attains 
an  average  diameter  of  six  to  eight  inches.  Trees  having  a  diameter 
of  three  feet  have  been  found.  Sargent  ("  Silva  of  North  America," 
vol.  2,  p.  37)  states  that  the  tree  attains  a  height  of  thirty-five  to 


Am.  Jour.  Pharm.  > 
September,  1914.  / 


Rhamnus  Purshiana. 


391 


forty  feet  with  a  diameter  of  eighteen  to  twenty  inches.  In  shady 
places  the  tree  grows  tall,  straight,  and  slender,  while  in  open  places 
with  plenty  of  sunlight  it  branches  near  the  base,  attains  greater 
diameter  and  less  height. 

A  mild,  moist  climate  is  necessary  for  the  abundant  growth  and 
large  size  of  the  tree.  In  a  dry  climate  and  higher  altitude  it  occurs 
sparingly  and  in  shrub  form  only.  In  its  most  northern  range,  in 
Southeastern  Alaska,  it  also  grows  as  a  shrub  of  three  to  six  feet  in 
height.  In  certain  sections  of  the  California  coast  it  has  a  height 
of  only  a  few  inches  with  prostrate  stems. 

Reforesting. — Opinion  differs  as  to  the  natural  reforesting  of 
cut-over  areas.  It  is  stated  by  some  that  a  new  growth  always 
springs  up  on  cut-over  areas,  providing  the  bark  is  not  removed  from 
the  stumps;  while  others  claim  that  sprouts  rarely  spring  up  from 
stumps,  because  the  trees  are  usually  cut  while  the  sap  is  running, 
hence  very  little  life  is  left  in  the  stump. 

The  tree  is  a  prolific  seeder ;  seeds  are  of  medium  high  germination 
(often  tardy)  and  of  very  persistent  vitality.  Scattered  seedlings 
are  fairly  abundant  in  moist  forests,  litter  and  mucky  soils  ;  scanty 
in  drier  habitat,  except  in  depressions  where  seeds  have  been  deeply 
covered  by  accident.  (Geo.  B.  Sudworth,  U.  S.  Department  of 
Agriculture,  Forest  Service  Bulletin,  "  Forest  Trees  of  Pacific  Slope," 
1908,  p.  404.) 

Longevity. — The  longevity  has  not  been  fully  determined  for 
large  trees.  Trees  ten  years  old  are  from  six  to  eight  inches  in 
diameter.  Trees  estimated  at  twenty-five  to  forty  years  old  are  fre- 
quently found. 

Cultivation. — For  several  years  the  U.  S.  Department  of  Agri- 
culture has  conducted  experiments  looking  towards  the  cultivation 
of  this  tree,  and  has  succeeded  in  growing  it  from  the  seed  in  moist 
places  near  Washington,  D.  C,  the  trees  in  six  years  from  the  seed 
attaining  a  height  of  ten  to  twelve  feet. 

The  Kew  Gardens  in  England  ten  years  ago  raised  cascara  sagrada 
from  the  seed  collected  in  California,  and  it  has  proved  quite  hardy. 
The  tree  has  also  been  grown  in  Germany,  but  is  said  to  develop  but 
slowly. 

In  the  experiments  conducted  by  the  Department  of  Agriculture  a 
certain  method  of  pruning  has  been  followed  which  forces  the  top  of 
the  tree  into  three  or  four  branches;  one  of  these  branches  may  be 
cut  each  year  for  peeling,  and,  as  another  branch  soon  develops  in  its 


392  Rhamnus  Purshiana.  {^S^dS^mA 

place,  this  will  be  ready  for  cutting  in  a  few  years,  the  other  branches 
in  the  meantime  having  been  treated  in  the  same  way. 

Seed  of  Rhamnus  Purshiana  is  not  on  the  market,  but  would 
have  to  be  collected  by  some  one  in  the  cascara  region.  (Alice  Henkel, 
"  The  Cultivation  of  Medicinal  Plants,"  The  Druggists'  Circular, 
March,  1912,  p.  133.) 

The  following  is  a  description  of  the  bark,  leaves,  flowers,  and  nut- 
lets of  Rhamnus  Purshiana  by  Sargent  ("  Silva  of  North  America," 
vol.  2,  pp.  37-40). 

The  bark  of  the  trunk,  even  on  old  trees,  is  rarely  more  than  a 
quarter  of  an  inch  thick,  and  varies  in  color  from  dark  brown  to 
light  brown  or  gray  tinged  with  red,  the  surface  being  broken  into 
short,  thin  scales.  The  branchlets,  when  they  first  appear,  are 
coated  with  fine,  soft  pubescence;  they  are  pale  yellow,  green,  or 
reddish-brown,  and  are  pubescent,  glabrous,  or  covered  with  scat- 
tered hairs  in  their  second  season,  when  they  are  marked  with  large, 
elevated  scars  left  by  the  falling  of  the  leaves. 

The  leaves  are  alternate,  elliptical-oblong,  obovate,  acuminate,  or 
broadly  elliptical,  and  are  obtuse,  acute,  or  bluntly  pointed  at  the 
apex,  rounded  sub-cordate,  or  sometimes  wedge  shaped  at  the  base, 
and  serrulate,  denticulate,  obscurely  crenate,  or  often  merely  entire 
with  wavy  margins.  They  are  thin  membranaceous  or  sometimes 
thick  and  coriaceous,  and  are  glabrous  or  pubescent  with  scattered 
hair  on  the  lower  surface  and  along  the  veins  on  the  upper  surface. 
They  vary  from  an  inch  to  over  seven  inches  in  length,  and  are  con- 
spicuously netted  veined,  with  broad  and  prominent  mid-ribs  and 
primary  veins  ;  they  are  borne  on  stout,  often  pubescent,  petioles 
one-half  inch  or  an  inch  long,  and  are  sometimes  pale  yellow-green 
above  and  below,  and  sometimes  dark  green  and  rather  opaque 
above  and  paler  and  often  somewhat  orange  color  or  brown  on  the 
lower  surface. 

In  Washington  and  Oregon  and  at  high  elevations  in  the  moun- 
tains the  leaves  fall  late  in  November,  having  previously  turned 
pale  yellow.  Farther  south  and  near  the  California  coast  they  re- 
main on  the  branches  almost  all  winter,  or  until  the  following 
spring.  The  stipules  are  membranaceous,  acuminate,  and  nearly 
deciduous. 

The  flowers  are  produced  on  the  young  shoots  in  axillary  um- 
bellate cymes  or  slender,  pubescent  peduncles  varying  from  one- 
half  to  nearly  an  inch  in  length.   The  pedicels  are  slender,  pubescent, 


Am.  Jour.  Pharm.  ) 
September,  1914.  J 


Rhamnus  Purshiana. 


393 


a  quarter  of  an  inch  to  almost  an  inch  long  and  four  to  five  times 
longer  than  the  calyx,  which  is  narrowly  campanulate  with  more 
or  less  spreading  acuminate  lobes.    The  petals  are  minute,  ovate, 


Fig.  2. — Peeling  Cascara  bark  in  Washington  forests.    Illustrating  a  method  employed  in 
commercial  collection,  and  the  dense  forest  in  which  the  collector  must  work. 

and  deeply  emarginate  at  the  apex,  and  enfold  the  short  stamens, 
whose  filaments  are  somewhat  thickened  at  the  base.  The  style 
is  crowned  with  a  slender  two-lobed  stigma.  The  fruit  globose  or 
broadly  obovoid,  a  third  to  one-half  inch  in  diameter  and  very 


394 


Rhamnus  Purshiana. 


Am.  Jour.  Pharm. 
September,  1914. 


slightly  or  not  at  all  lobed,  with  thin,  rather  juicy  pulp  and  two  or 
three  nutlets.  It  is  at  first  green,  then  red,  and  finally  black  at 
maturity. 


Fig.  3. — Cutting  Cascara  tree  in  Washington  forests. 

The  nutlets  are  obovate,  usually  a  third  to  an  inch  long,  rounded 
on  the  back,  and  flattened  on  the  inner  surface  by  mutual  pressure, 
with  two  bony,  tooth-like  enlargements  at  the  base,  one  on  each 
side  of  the  large  scar  of  the  hilum,  and  a  thin  gray  or  pale  yellow- 


Am.  Jour.  Pharm.  ) 
September,  1914.  J 


Rhamnus  Purshiana. 


395 


green  shell.  The  testa  of  the  seed  is  thin  and  papery,  its  outer 
surface  of  a  yellow-brown  color  and  its  inner  surface  like  the 
cotyledons,  bright  orange  color. 

Characteristics  of  the  Wood. — The  wood  of  Rhamnus  Pur- 
shiana while  green  is  soft  and  brittle,  but  when  dry  it  is  tough  and 
hard.  After  the  bark  is  removed  from  the  wood  it  checks  very 
easily  on  drying.  It  is  used  to  some  extent  in  making  ax-handles 
and  wagon  spokes. 

Collection  of  Bark. — The  season  for  peeling  and  collection  of 
the  bark  is  during  the  months  of  April  to  September.  The  tree  is 
usually  cut  down  and  the  bark  removed  from  every  part  except 
the  smallest  branches.  Trees  of  four  inches  or  less  in  diameter 
are  not  cut,  because  the  bark  is  too  thin.  Foreign  material,  such  as 
sand,  moss,  etc.,  is  removed  by  scraping;  the  common  curry  comb 
is  the  convenient  tool.  Those  who  peel  on  a  small  scale  usually 
prepare  very  clean  bark,  while  those  who  work  on  a  larger  scale  are 
frequently  careless  in  removing  foreign  matter.  Much  of  the  bark 
is  collected  by  small  ranchers  and  Indians  living  in  the  vicinity  of  the 
cascara  areas.  Larger  quantities  are  collected  by  companies,  who 
•  employ  a  number  of  men  for  this  purpose  during  the  season  of 
collection. 

Curing  of  the  Bark. — After  being  mossed  the  bark  is  spread  out 
on  the  ground  on  tarpaulins  or  on  racks  in  the  sunshine  to  cure. 
Sometimes  it  is  kept  under  cover  during  the  curing  period.  If  placed 
in  direct  sunlight  it  usually  takes  about  four  days  for  the  curing 
process.  About  60  per  cent,  of  its  weight  is  lost  during  the  curing 
stage.  If  not  rained  upon  the  bark  will  cure  with  a  rich  satin  brown 
color,  while  if  rained  upon  it  will  be  spotted  with  black  or  become 
entirely  black.  Slow,  careful  drying  yields  bark  10  per  cent,  heavier 
than  if  hastily  dried.  The  bark  when  dry  is  broken  into  small  pieces, 
usually  by  means  of  a  feed  chopper,  then  packed  into  sacks  holding 
from  50  to  100  pounds  and  stored  in  a  dry  place.  The  collector  of 
the  bark  seldom  keeps  it  during  the  aging  period  of  one  to  two 
years.  The  season's  collection  is,  as  a  rule,  contracted  for  before 
peeling  begins,  and  the  product  is  shipped  early  in  the  fall.  The 
dried  bark  must  be  carefully  kept,  otherwise  it  will  absorb  moisture 
and  deteriorate. 

Prices  and  Production. — When  first  introduced  to  commerce 
the  bark  of  cascara  sagrada  commanded  a  price  of  fifty  to  sixty  cents 
per  pound.    The  supply,  however,  rapidly  increased  and  prices  fell 


396 


Rhamnus  Purshiana. 


(  Am.  Jour.  Pharm. 

\  September,  1914. 


during  the  next  few  years.  The  following  table  presents  data  on 
prices  and  annual  production  of  the  bark  for  the  last  decade,  as 
compiled  from  the  files  of  the  Oil,  Paint  and  Drug  Reporter  by 
Rodney  H.  True  (The  Pharmaceutical  Era,  January,  1913,  p.  9)  : 


Year. 

Highest  price 

Lowest  price 

Estimated  quantity 

per  pound. 

per  pound. 

of  bark  peeled. 

  5-5 

cents 

4-5 

cents 

500-600  tons. 

1902  

  6.0 

cents 

4.75  cents 

450  tons. 

1903. • •  •  

  22.5 

cents 

10.0 

cents 

1000  tons. 

1904  

  17.00  cents 

7.0 

cents 

750-1500  tons. 

1905  

  7-0 

cents 

5.5 

cents 

850  tons. 

IOX)6  

  11.0 

cents 

5.5 

cents 

200  tons. 

I907  

  10.5 

cents 

8.5 

cents 

250-600  tons. 

1908  

  9-5 

cents 

6.5 

cents 

I909  

  8.5 

cents 

7.0 

cents 

I9IO  

  7-5 

cents 

7.0 

cents 

550-^600  tons. 

I9II  

  90 

cents 

7.5 

cents 

1000-2000  tons. 

1912  

  10.5 

cents 

8.0 

cents 

500  tons. 

Stewart  &  Holmes  Drug  Company,  of  Seattle,  Wash.,  states 
that  the  average  price  of  the  bark  on  the  Pacific  coast  for  1913  was 
5  cents  per  pound,  and  the  yield  was  estimated  at  1200  to  1500  tons. 
It  is  estimated  that 'about  50  per  cent,  of  the  annual  yield  is  ex- 
ported to  Europe,  the  remainder  being  shipped  to  eastern  drug 
manufacturers  of  the  United  States. 

Future  Supply. — Cascara  dealers  have  been  predicting  for 
more  than  a  quarter  of  a  century  that  the  supply  would  soon  be 
exhausted,  but  each  year  the  yield  is  sufficient  to  meet  the  demand. 
The  greater  portion  of  the  easily  accessible  trees  have  been  cut, 
therefore  the  collectors  must  find  new  fields,  which  are  naturally 
more  remote  from  transportation. 

Collectors  usually  leave  standing  trees  under  four  inches  in 
diameter,  because  of  the  thin  bark,  which  insures  reproduction  on 
cut-over  areas.  The  vast  holdings  of  large  timber  companies  con- 
tain thousands  of  tons  of  cascara,  but  they  will  not  permit  the 
peeling  of  these  trees.  This  fact,  together  with  the  fact  that  new 
trees  are  growing  on  tracts  that  have  been  peeled  once  or  twice 
before,  insures  a  supply  of  bark  for  many  years. 

Description  of  the  Cured  Bark. — It  is  usually  in  flattened  or 
transversely  curved  pieces,  occasionally  in  quills  two  to  ten  centi- 
metres long,  and  three  centimetres  in  diameter,  bark  one  to  three 
millimetres  thick;  outer  surface  dark  brown  or  brownish  red,  fre- 
quently completely  covered  with  grayish  or  whitish  lichens,  several  of 


Am.  Jour.  Pharm. ) 
September,  1914.  j 


Rhamnus  Purshiana. 


397 


which  are  peculiar  to  this  bark,  and  with  small  groups  of  brownish 
apothecia,  longitudinally  striate,  turning  red  when  moistened  with 
solutions  of  the  alkalies;  fracture  short,  with  projections  of  bast 
fibres  in  the  inner  bark,  the  medullary  rays  one  or  two  cells  wide, 
forming  converging  groups ;  in  cross  section  this  inner  surface  of 
the  bark  indistinctly  crenate ;  odor  distinct ;  taste  bitter,  slightly  acrid. 
(Dr.  Henry  Kraemer,  "  Botany  and  Pharmacognosy,"  3rd  Edition, 
P-  524.) 


Fig.  4. — Packing  Cascara  bark  to  trail.    Because  of  the  underbrush  and  fallen  timber  horses 
cannot  be  used  except  on  trails. 


Description  of  the  Powdered  Bark. — The  powdered  bark  is 
light  brown ;  bast  fibres  long,  much  thickened,  lignified ;  stone  cells 
very  thick-walled,  about  50  fi  in  diameter,  crystal  fibres  containing 
monoclinic  Crystals  of  calcium  oxalate;  calcium  oxalate  also,  in 
rosette  aggregates  or  monoclinic  prisms  5  to  20  fx  in  diameter ;  starch 
grains  spherical,  about  4  ^  in  diameter;  parenchymatous  cells  with 
yellowish  contents  colored  red  with  alkalies.  (Dr.  Henry  Kraemer, 
"  Botany  and  Pharmacognosy,"  3rd  Edition,  p.  759.) 

Structure  of  the  Bark.— The  bark  as  described  by  Prescott 
consists  of  three  parts ;  namely,  the  corky  layer,  the  middle  bark,  and 
the  inner  bark. 


398 


Rhamnus  Purshiana. 


f  Am.  Jour.  Pharm. 
(  September,  1914. 


The  corky  layer  consists  of  an  outer  epidermis  of  dark  brown 
weathered  cells,  then  several  rows  of  cells  filled  with  a  dark  red 
coloring  matter,  and  in  the  more  recent  bark  a  row  or  two  of  cells 
containing  chlorophyll. 

The  middle  bark  is  made  up  of  parenchymatous  cells,  which  are 
filled  with  small  starch  grains.  There  are  visible,  also,  in  the  trans- 
verse section,  several  groups  of  cubical  crystals  and  in  the  longitudinal 
section  groups  of  very  thick-walled  yellow  cells. 

The  inner  bark  consists  principally  of  yellow  medullary  rays, 


Fig.  5- — Transporting  Cascara  bark  on  pack  horses  to  wagon  road. 


separated  by  bast  parenchyma,  through  which  are  scattered  numerous 
yellow  bast  fibres.  As  seen  in  the  longitudinal  section,  these  fibres 
are  frequently  surrounded  by  small  cubical  crystals.  (Parke,  Davis 
and  Company,  "  New  Preparations,"  Feb.  5,  1879;  "  Proc.  of  Amer. 
Pharm.  Assoc.,"  vol.  27,  1879,  p.  262.) 

Microscopical  Examination  of  the  Bark. — The  corky  layer 
is  about  0.045  mm-  thick,  and  consists  of  eight  or  twelve -rows,  some- 
what flattened,  rather  thick-walled,  but  not  sclerotic  cells.  The 
parenchyma  of  the  primary  bark  is  tangentially  elongated,  partly  of  a 
collenchymatic  character,  free  from  secondary  cork,  and  contains 


Am.  Jour.  Pharm. ) 
September,  1914.  j 


Rhamnus  Purshiana. 


399 


scattered  groups  of  roundish  stone  cells,  with  very  thick  walls,  and 
accompanied  by  single  rhombohedric  crystals ;  the  thin-walled  paren- 
chyma contains  numerous  groups  of  crystals.  The  inner  bark  con- 
sists of  medullary  rays  composed  of  two  or  three  rows  of  thin-walled, 
somewhat  radially  elongated  cells,  and  of  broader  bast  rays  in  which 
the  parenchyma  cells  are  coarsely  dotted  upon  the  radial  and  horizon- 
tal walls,  and  loosely  united  in  a  tangential  direction ;  the  sieve-tubes 
are  larger,  irregularly  angular,  and  united,  to  the  number  of  four  or 
six,  by  means  of  coarsely  porous  sieve-plates,  and  on  the  radial  sides 
marked  with  roundish  sieve  fields;  the  bast  fibres  form  alternate 
groups  of  two  or  three  rows,  extending  into  few  bast  rays,  and  are 
surrounded  by  crystal  cells.  (Dr.  J.  Moeller,  Pharm.  Centralhalle, 
No.  28,  1882;  11  Proc.  A.  Ph.  A.,"  vol.  31,  1883,  p.  166.) 

History  of  Rhamnus  Purshiana  in  the  Medical  Profession. 
— J.  Winchell  Forbes  {Practical  Druggist,  Aug.,  19 10,  p.  48)  states 
that  cascara  bark  was  brought  to  the  notice  of  the  public  in  1872  by  a 
man  named  Donnelly,  who  learned  of  its  virtues  from  the  Catholic 
priests  and  Indians  of  Oregon  and  northern  California.  The  priests 
called  the  tree  "  shittim  wood,"  claiming  that  it  was  identical  with 
that  used  in  making  the  Holy  Ark,  and  for  this  reason  the  bark  was 
called  cascara  sagrada  (sacred  bark) . 

Under  the  direction  of  Mr.  Forbes,  Donnelly  made  a  preparation 
of  the  bark  by  macerating  it  in  cider  vinegar  for  two  weeks.  This 
preparation  was  sold  as  a  patent  medicine  under  the  name  of 
"  Donnelly's  Discovery,"  which  appears  to  have  been  the  earliest 
commercial  use  of  the  bark. 

In  a  paper  contributed  to  "  New  Preparations  "  (Parke,  Davis 
and  Company,  Oct.  15,  1877,  p.  8),  Dr.  J.  H.  Bundy,  an  eclectic 
physician  of  Colusa,  Cal.,  commended  cascara  sagrada  as  a  valuable 
remedy  in  the  treatment  of  constipation.  In  January,  1878,  Dr. 
Bundy  contributed  a  paper  on  the  subject  of  cascara  sagrada  in  which 
he  gave  the  uses  of  its  fluidextract. 

To  Dr.  J.  H.  Bundy,  1877,  is  due  the  credit  of  introducing  the 
bark  of  Rhamnus  Purshiana  (cascara  sagrada)  to  the  medical  pro- 
fession. In  1877  he  shipped  a  quantity  of  the  bark  to  Parke,  Davis 
and  Company,  of  Detroit,  Mich.,  who  in  1878  made  the  first  phar- 
maceutical preparation  (the  fluidextract).  To  Parke,  Davis  and 
Company  is  therefore  due  the  credit  of  bringing  a  preparation  of  this 
drug  to  the  attention  of  physicians  and  pharmacists.  Parke,  Davis 
and  Company  were  for  a  number  of  years  the  sole  manufacturers  of 


40o 


Rhamnus  Purshiana. 


I  Am.  Jour.  Pharin. 
\  September,  1914. 


preparations  of  this  drug.  ("  Proc.  of  the  Amer.  Pharm.  Assoc.," 
vol.  44,  1896,  p.  198 ;  Practical  Druggist,  August,  1910,  p.  48 ;  Bulletin 
of  the  Lloyd  Library,  No.  18,  191 1,  pp.  68,  69.) 

Parke,  Davis  and  Company  state  in  one  of  their  publications  that 
they  brought  cascara  sagrada  to  the  notice  of  the  British  Medical 
Association  at  Cork  in  1879. 

Dr.  C.  H.  Adair,  of  Colusa,  Cal.,  a  partner  of  Dr.  Bundy,  sent, 
in  1878,  specimens  of  the  bark  and  botanical  specimens  of  the  tree 
yielding  it  to  J.  U.  Lloyd,  of  Cincinnati,  Ohio.  These,  on  identifica- 
tion by  Curtis  G.  Lloyd,  proved  to  be  Rhamnus  Purshiana,  thus 
establishing  the  drug's  botanical  position.  ("  Proc.  of  the  Amer. 
Pharm.  Assoc.,"  vol.  44,  1896,  p.  198;  Bulletin  of  the  Lloyd  Library, 
No.  18,  191 1,  p.  70.) 

In  1880  George  W.  Kennedy  first  published  a  formula  for  an  elixir 
of  Rhamnus  Purshiana.  ("  Proc.  of  the  Amer.  Pharm.  Assoc.," 
vol.  28,  1880,  p.  431.) 

Prof.  W.  T.  Wenzell,  in  1883,  published  a  formula  for  an  elixir  of 
cascara  sagrada,  using  potassium  carbonate  to  remove  the  bitter  prin- 
ciple. ("  Proc.  of  the  Cal.  Pharm.  Soc,"  1883;  Amer.  Jour,  of 
Pharm.,  May,  1883,  p.  252;  "  Proc.  of  the  Amer.  Pharm.  Assoc.," 
vol.  31,  1883,  p.  82.) 

Mr.  James  G.  Munson,  a  druggist  of  San  Jose,  Cal.,  in  a  letter 
to  the  writers  under  date  of  January  24,  1914,  claims  to  have  been 
the  first  to  discover  how  to  make  tasteless  fluidextract  of  cascara 
sagrada  by  the  magnesium  oxide  process.  This  was  in  the  fall  of 
1886,  while  he  was  in  the  employ  of  Prof.  W.  M.  Searby,  of  San 
Francisco,  Cal.  Mr.  Munson,  however,  did  not  publish  a  formula 
for  the  preparation,  and  the  method  remained  a  trade  secret.  (The 
Pacific  Druggist,  June  15,  1890,  p.  27.) 

Dr.  Fred  A.  Grazer,  of  Sacramento  County  Hospital,  Sacramento, 
Cal.,  in  a  letter  to  the  writers  under  date  of  November  21,  1913, 
states  that  Prof.  W.  M.  Searby,  of  San  Francisco,  Cal.,  was  the  first 
to  introduce  a  preparation  of  bitterless  fluidextract  of  cascara  sagrada 
which  was  offered  for  sale  by  retail  druggists.  The  method  of  manu- 
facture was  a  secret  process,  no  formula  being  published.  Dr.  Grazer 
published  the  first  formula  for  the  preparation  of  a  bitterless  fluid- 
extract  of  cascara  sagrada,  using  calcined  magnesia  to  remove  the 
bitter  principle.  (P  har  mac  cutis  che  Rundschau,  Jan.,  1888,  p.  9; 
"  Proc.  of  the  Amer.  Pharm.  Assoc.,"  vol.  36,  1888,  p.  253.) 

Parke,  Davis  and  Company,  of  Detroit,  Mich.,  in  their  pamphlet 


Am.  Jour.  Pharm.  1 
September,  1914.  J 


Rhamnus  Purshiana. 


401 


on  "  Cascara  Sagrada  and  its  Preparation,"  state  that  they  have  a 
formula  (No.  536),  under  date  of  1887,  for  the  manufacture  of 
aromatic  (tasteless)  fluid  cascara  sagrada. 

R.  Wright  published,  in  1888,  a  formula  for  a  bitterless  fluid- 
extract  of  cascara  sagrada,  .using  calcined  magnesia  to  remove  the 
bitter  principle.  ("  Yearbook  of  Pharmacy,"  1888,  pp.  395,  396; 
"  Proc.  of  the  Amer.  Pharm.  Assoc.,"  vol.  37,  1889,  p.  381.) 

Prof essor  John  M.  Maisch  ("  Proc.  of  the  Amer.  Pharm.  Assoc.," 
vol.  38,  1890,  p.  394)  calls  attention  to  the  fact  that  H.  R.  Slack,  Jr., 


Fig.  6. — Sun-drying  Cascara  bark  on  platform  of  abandoned  saw-mill. 


recently  recommended  Rhamnus  Purshiana  for  pharmacopceial  recog- 
nition before  the  Georgia  Pharmaceutical  Association. 

The  bark  first  became  official  in  the  United  States  Pharmacopoeia 
in  the  1890  edition. 

History  of  the  Chemistry  of  Rhamnus  Purshiana. — The 
first  chemical  examination  of  the  bark  was  made  by  Dr.  A.  B. 
Prescott,  who  isolated  a  brown  resin  of  strong,  bitter  taste,  colored 
vivid  purple- red  by  potassium  hydroxide  solution ;  a  red  resin,  nearly 
tasteless,  colored  rich  brown  by  potassium  hydroxide  solution ;  a 
yellow  resin  or  a  neutral  body,  tasteless,  colored  bright  red-brown  by 
sulphuric  acid,  not  colored  by  potassium  hydroxide  solution.   He  also 


402 


Rhamnus  Purshiana. 


(  Am.  Jour.  Pharm. 
(  September,  1914.. 


isolated  a  crystallizable  body  in  white  double  pyramids,  and  some 
other  form  of  dimetric  system.  Tannic  acid,  oxalic  acid,  malic  acid, 
a  fixed  oil,  a  volatile  oil,  wax,  and  starch  were  also  found.  (Amer. 
Jour,  of  Pharm.,  vol.  51,  1879,  P-  I^>5-) 

Limousin  (Jour,  de  Pharm.  et  de  Chim.  (5),  vol.  6,  1885,  p.  80; 
"  Proc.  of  the  Amer.  Pharm.  Assoc.,"  vol.  33,  1885,  p.  188)  con- 
sidered that  the  resins  obtained  by  Prescott  were  derived  from 
chrysophanic  acid,  which  he  believed  to  be  present  in  notable  quan- 
tities. According  to  H.  A.  D.  Jowett  ("  Proc.  of  the  Amer.  Pharm. 
Assoc.,"  vol.  52,  1904,  p.  288)  these  deductions  are  incorrect.  He 
believes  that  emodin,  which  he  claims  is  present,  will  give  the  char- 
acteristic reactions  thought  to  be  due  to  chrysophanic  acid. 


Fig.  7- — A  means  of  moving  dried  Cascara  bark  to  bark  cutter. 


W.  T.  Wenzell  (Pharm-.  Runds.,  vol.  4,  1886,  p.  79)  isolated  from 
the  bark  a  small  quantity  of  an  orange-red,  crystalline  substance, 
melting  at  226°-230°  C,  and  having  the  properties  of  a  glucoside. 
Later  investigators  have  shown  that  it  was  impure  emodin. 

H.  F.  Meier  and  J.  L.  Webber  (Amer.  Jour,  of  Pharm.,  vol.  60, 
1888,  p.  87)  found,  as  a  result  of  their  investigation,  a  glucoside,  a 
ferment,  glucose,  and  traces  of  ammonia. 

Paul  Schwabe  (Archiv,  der  Pharm.,  vol.  226,  1888,  p.  569)  ex- 
amined Rhamnus  Purshiana  and  found  emodin,  identical  with  that  of 
Rhamnus  frangula,  to  exist  as  such  in  the  bark,  and  identified  it  by 
means  of  its  acetyl  and  di-bromo  compounds,  all  of  which  were 


Am.  Jour.  Pharm. ) 
September,  1914.  / 


Rhamnus  Purshiana. 


403 


analyzed.  He  considered  that  Wenzell's  crystals,  previously  referred 
to,  were  merely  impure  emodin,  and  could  obtain  no  evidence  of  the 
existence  of  a  glucoside,  nor  could  he  isolate  any  other  crystalline 
substance. 

Dr.  Eccles  reports  in  the  Druggists  Circular  of  March,  1888, 
p.  54,  the  discovery  of  the  presence  of  an  alkaloid  which  he  states  he 
has  separated  from  the  fluidextract  and  precipitated  by  Mayer's 
reagent. 

A.  C.  Zeig  ("  Proc.  of  the  Amer.  Pharm.  Assoc.,"  vol.  37,  1889, 
p.  261 )  further  examined  the  resins  previously  described  by  Prescott, 
but  was  unable  to  isolate  any  definite  principle. 

Le  Prince  (Compt.  rend.,  vol.  115,  1892,  p.  286)  claims  to  have 
obtained  the  active  principle  of  cascara  bark  in  a  crystalline  form  and 
named  it  cascarine.  Le  Prince  suggested  that  cascarine  might  be 
identical  with  rhamnetin. 

A  most  curious  confusion  has  arisen  in  chemical  literature  with 
respect  to  this  substance.  Beilstein  ("  Handbuch,"  3rd  edition,  vol.  3, 
p.  627),  under  cascarine,  states  that  it  is  identical  with  rhamnetin, 
but  Phipson  (Compt.  rend.,  vol.  115,  1892,  474)  considers  that  it  was 
identical  with  xantho-rhamnin,  and  Van  Rijn  ("  Die  Glykoside," 
1900  edition,  p.  299),  without  comment,  accepts  this  latter  statement, 
and  under  xantho-rhamnin  gives  the  details  of  Le  Prince's  prepara- 
tion of  cascarine  from  cascara, 

The  properties  of  cascarine,  as  given  by  Le  Prince,  prove  that  it 
could  not  be  identical  with  either  rhamnetin  or  xantho-rhamnin. 
Le  Prince  presents  no  evidence  of  the  purity  of  cascarine ;  it  agrees, 
however,  in  properties,  with  the  exception  of  the  melting-point,  with 
emodin. 

E.  Cabanes  states  that  the  active  principles  of  cascara  bark  are 
located  in  the  layers  of  bast  immediately  adjoining  the  cambium,  and 
in  the  medullary  rays  traversing  these  layers.  {Pharm.  Jour.,  May  2, 
1896,  p.  343 ;  Rep.  de  Pharm.  (3),  vol.  7,  p.  97 ;  "  Proc.  of  the  Amer. 
Pharm.  Assoc.,"  vol.  44,  1896,  p.  638.) 

A.  R.  L.  Dohme  and  H.  Englehardt  ("  Proc.  of  the  Amer.  Pharm. 
Assoc.,"  vol.  45,  1897,  p.  193)  examined  Rhamnus  Purshiana  and 
claimed  to  have  isolated  the  active  principle  of  the  drug,  which  they 
named  Purshianin.  This  was  stated  to  be  a  glucoside,  yielding,  on 
hydrolysis,  emodin  and  a  sugar  which  was  not  identified.  They  con- 
sider the  fat  to  be  a  mixture  of  dodecyl  palmitate  and  stearate.  They 
also  attempted  to  obtain  the  bitter  principle  in  a  crystalline  form,  but 
were  unsuccessful. 


404 


Rhamnus  Purshiana. 


l  Am.  Jour.  Pharm. 
\  September,  1914. 


H.  A.  D.  Jowett  ("  Proc.  of  the  Amer.  Pharm.  Assoc.,"  vol.  52, 
1904,  p.  295)  summarizes  the  results  of  previous  investigators  as 
follows : 

I.  The  only  definite  principle  isolated  from  cascara  bark,  the 
identity  of  which  can  be  considered  to  be  absolutely  established,  is 
emodin. 

2.  The  statement  of  the  existence  in  the  bark  of  chrysophanic  acid, 
chrysarobin,  or  glucosides  yielding  on  hydrolysis  emodin,  chryso- 
phanic acid,  or  rhamnetin,  is  not  supported  by  satisfactory  experi- 
mental evidence. 


Fig.  8. — Cutting  and  sacking  dried  Cascara  bark. 


3.  Wenzell's  "  crystals,"  Le  Prince's  "  Cascarine,"  and  Dohme 
and  Engelhardt's  "  Purshianin  "  would  appear,  from  the  descriptions 
given  by  the  respective  authors,  to  be  merely  impure  emodin. 

4.  No  indication  can  be  given  of  the  identity  of  the  crystals 
described  by  Prescott. 

5.  It  has  been  stated  by  Dohme  and  Engelhardt  that  the  fat  of 
cascara  consists  of  dodecyl  palmitate  and  stearate. 

Mr.  Jowett  ("  Proc.  Amer.  Pharm.  Assoc.,"  vol.  52,  1904, 
pp.  288-295),  in  his  investigations,  confirmed  the  presence  of  emodin 
in  cascara,  and  also  isolated  a  substance  which  he  called  isoemodin. 
He  also  found  glucose  and  syringic  acid.  No  evidence  was  obtained 
of  the  existence  of  chrysophanic  acid,  chrysarobin,  or  glucosides 
yielding  on  hydrolysis  emodin,  chrysophanic  acid,  or  rhamnetin. 


Am.  Jour.  Tharm. ) 
September,  1914.  J 


Rhamnus  Purshiana. 


405 


No  substance  corresponding  to  either  cascarine  or  purshianin  was 
found.  The  fat  was  found  to  consist  of  rhamnol  arachidate  and  free 
arachidic  acid.  A  hydrolytic  enzyme  was  isolated.  The  bitter  and 
the  active  principles  of  the  bark  were  not  isolated. 

Chemical  Constituents. — The  chemical  constituents  of 
Rhamnus  Purshiana  are  being  studied  by  the  writers,  and  the  results 
of  the  investigation  will  appear  in  a  later  issue  of  this  journal. 

Acknowledgments. — The  authors  wish  to  express  appreciation 
to  Dr.  John  Uri  Lloyd,  of  the  Lloyd  Library,  Cincinnati,  Ohio,  and 
Dr.  John  M.  Francis,  of  Parke,  Davis  and  Company,  Detroit, 
Mich.,  for  historical  facts ;  to  Prof.  Hugo  Winkenwerder,  dean  of 
the  University  of  Washington  College  of  Forestry,  for  facts  con- 
cerning Rhamnus  Purshiana  in  the  State  of  Washington ;  to  Dr.  Fred 
A.  Grazer,  of  Sacramento,  Cal.,  and  Mr.  James  G.  Munson,  of 
San  Jose,  Cal.,  for  facts  relating  to  the  first  bitterless  preparations 
of  the  bark ;  to  Mr.  Floyd  E.  Ryus,  of  Ketchikan,  Alaska,  for  in- 
formation concerning  the  growth  of  the  tree  in  Alaska ;  to  Mr.  Carl  L. 
Kurtz,  of  Notus,  Idaho,  for  information  concerning  its  growth  and 
range  in  Idaho;  to  Mr.  H.  E.  Holmes,  of  Stewart  &  Holmes  Drug 
Company,  Seattle,  Wash. ;  Mr.  Geo.  D.  Prigmore,  a  druggist,  of  Che- 
halis,  Wash.,  and  Mr.  Charles  A.  Richey,  of  Seattle,  Wash. ,  for  data 
concerning  the  growth  of  the  tree  and  collection  of  the  bark  in 
Washington. 

BIBLIOGRAPHY. 

Year. 

1775.  Rhamnus  alnifolia,  named  by  C.  L.  de  Brutelle  L'Heritier  in  1775. 
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1814.  Rhamnus  alnifolia,  named  by  Frederick  Pursh  in  1814.  Flora  Amer- 
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1888.    Cascara  Sagrada,  Presence  of  an  Alkaloid,  by  Dr.  R.  G.  Eccles. 

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Pharm.,  vol.  24,  1889,' p.  118. 
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1889.  Rhamnus  Purshiana,  Recommended  for  Pharmacopceial  Recognition, 

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Druggist,  June  15,  1890. 
1890.    Rhamnus    Purshiana,    Distinction    from    Rhamnus    Californica,  by 

Katharine  Brandegee.   Amer.  Jour,  of  Pharm.,  vol.  62,  1890,  p.  532 ; 

Pharm.  Rec,  Feb.  19,  1891,  pp.  71,  72  (from  "  Zoe,"  A  Biol.  Jour.)  ; 

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1891.    Rhamnus  Purshiana,  Notes  on  North  American  Trees,  by  Sargent. 

Garden  and  Forest,  vol.  23,  Feb.  18,  p.  75 ;  Pacific  Druggist,  April 
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1891.  Rhamnus  Purshiana,  Use  in  Mexico.  Amer.  Jour,  of  Pharm.,  vol.  63, 
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1891.    Cascara  Sagrada,  Aqueous  Liquidextract  of,  by  John  Moss.  Chem. 

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1891.  Cascara  Sagrada,  Tasteless  Extract  of,  by  G.  Hell.    Pharm.  Post, 

1891,  p.  729;  Proc.  Amer.  Pharm.  Assoc.,  vol.  40,  1892,  p.  452. 

1892.  Cascara  Sagrada,  Extract  of,  by  N.  J.  Pritzker.    Apothecary,  Feb., 

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1892.    Cascara  Sagrada,  Cascarin,  The  Active  Principle  of,  by  M.  Le  Prince. 

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1892.  Cascara  Sagrada,  Cascarin,  by  Phipson.  Compt.  rend.,  vol.  115,  1892, 
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Pharm.  Assoc.,  May,  1892;  Proc.  Amer.  Pharm.  Assoc.,  vol.  41, 

1893,  P-  477- 

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1894.  Cascara   Sagrada,   Bitterless   Fluidextract  of,  by  F.   Edel.  Amer. 

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1896.  Cascara  Sagrada,  History  and  Names  of,  by  John  Uri  Lloyd.  Amer. 

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4io  Rhamnus  Purshiana.  {^Xrfiiw 

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1896.  Cascara  Sagrada,  Aromatic  Fluidextract  of,  Use  of  Lime,  first  sug- 

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1897.    Cascara  Sagrada,  Review  of  Previous  Experiments,  by  L.  F.  Stevens. 

Proc.  N.  Y.  State  Pharm.  Assoc.,  1897,  pp.  246-49;  Proc.  Amer. 
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1898.  Rhamnus   Purshiana,   Impurity  of  the   Bark,  by  Holmes.  Pharm. 

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1898.  Cascara  Sagrada,  Bitter  Principle  of,  by  A.  R.  L.  Dohme  and  H. 

Engelhardt.  Amer.  Jour.  Pharm.,  vol.  70,  Sept.,  1898,  p.  480;  Proc. 
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1899.  Cascara  Sagrada,  Aromatic  Fluidextract  of,  by  E.  H.  La  Pierre.  Proc. 

Mass.  State  Pharm.  Assoc.,  1899,  p.  54 ;  Proc.  Amer.  Pharm.  Assoc., 
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1900.  Cascara  Sagrada,  Acetic  Fluidextract  of,  by  Dr.  E.  R.  Squibb.  Amer. 

Jour.  Pharm.,  July,  1900,  pp.  311-19;  Proc.  Amer.  Pharm.  Assoc., 
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1900.    Rhamnus  Purshiana,  Xantho-rhamnin,  by  Van  Rijn.    Die  Glykoside, 
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Am.  Jour.  Pharm.  ) 
September,  1914.  / 


Rhamnus  Purshiana. 


411 


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1903.  Rhamnus  Purshiana,  Description  of  Tree,  by  Thomas  Howell.  Flora 

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1904.  Cascara  Sagrada,  Chemical  Examination  of  Bark,  by  H.  A.  D.  Jowett. 

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1905.  Cascara  Sagrada,  Aromatic  Fluidextract  of,  Adopted  in  the  Com- 

pendium of  Canadian  National  Formulary.  Pharmaceutical  Era, 
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1905.    Cascara  Sagrada,  Bitterless  Extract,  Loss  of  Active  Matter,  by  Pan- 

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Proc.  Amer.  Pharm.  Assoc.,  vol.  54,  1906,  p.  628. 
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Pharm.  Era,  Aug.  17,  1905,  pp.  150,  151;  Proc.  Amer.  Pharm.  Assoc., 

vol.  54,  1906,  p.  794. 

1905.  Cascara  Sagrada,  Method  of  Gathering  and  Curing  in  Oregon,  by  J. 

Lee  Brown.  Western  Druggist,  Nov.,  1905,  p.  701 ;  Proc.  Amer. 
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1906.  Cascara  Sagrada,  Fluidextract,  U.  S.  P.,  Alcohol  in,  by  Joseph  Feil. 

Proc.  Ohio  State  Pharm.  Assoc.,  1906,  p.  48;  Proc.  Amer.  Pharm. 
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Henkel.    Bureau  of  Plant  Industry,  U.  S.  Dept.  Agri.,  Bui.  89, 
.  1906,  p.  58. 

1906.  Cascara  Sagrada,  Tasteless  Preparation  of,  by  H.  Knopf.  Chem. 

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1907.  Cascara  Sagrada,  Note  on  Fluidextract  of,  by  C.   Symes.  Amer. 

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1907.    Cascara  Sagrada,  Bitterless,  Effect  of  Magnesia  not  Detrimental,  by 


412 


Rhamnus  Purshiana. 


(  Am.  Jour.  Pharni. 
\  September,  1914. 


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1907.    Cascara  Sagrada,  Improved  Formula  for  Liquidextract  of,  by  J.  H. 

Franklin.  Trans.  Brit.  Pharm.  Conf.  (Yearbook  of  Pharm.), 
1907,  pp.  433,  434;  Proc.  Amer.  Pharm.  Assoc.,  vol.  56,  1908,  p.  84. 

1907.    Cascara  Sagrada,  Fluidextract  of,  Inefficiency  of  Identity  Test  G.  P. 

IV,  by  H.  Kroeber.  Pharmac.  Praxis,  No.  11,  1907;  Pharm.  Ztg., 
vol.  53,  1908,  p.  99;  Proc.  Amer.  Pharm.  Assoc.,  vol.  56,  1908,  p.  84. 

1907.  Cascara  Evacuant,  a  Preparation,  by  Parke,  Davis  and  Company. 

Amer.  Jour.  Pharm.,  vol.  79,  1907,  p.  117. 

1908.  Cascara  Sagrada,  Forest  Trees  of  Pacific  Slope,  by  Geo.  B.  Sudworth. 

Forest  Service  Bulletin,  1908,  p.  404,  U.  S.^Dept.  of  Agri. 
1908.    Rhamnus  Purshiana,  Description  of  Bark,  by  Dr.  Henry  Kraemer. 

Botany  and  Pharmacognosy,  3rd  ed.,  1908,  p.  524. 
1908.    Cascara  Sagrada,  Fluidextract  of,  Microscopic  Method  of  Distinction 

from  Fluidextract  of  Rhamnus  Fragula,  by  R.  Reutsh.  Pharm. 

Post,  No.  24,  1908;  Pharm.  Ztg.,  vol.  53,  1908,  p.  278;  Proc.  Amer. 

Pharm.  Assoc.,  vol.  56,  1908,  p.  85. 
1908.    Cascara  Sagrada,  Liquidextract  of,  Modification  of  B.  P.  Process,  by 

F.  Goldby.   Pharm.  Jour.,  Dec.  26,  1908,  p.  838 ;  Proc.  Amer.  Pharm. 

Assoc.,  vol.  57,  1909,  p.  79. 
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Quant.    Amer.  Jour,  of  Pharm.,  vol.  80,  Nov.,  1908,  p.  524;  Trans. 

Brit.  Pharm.  Conf.  (Yearbook  of  Pharm.),  1908,  pp.  519-21;  Proc. 

Amer.  Pharm.  Assoc.,  vol.  57,  1909,  p.  80. 

1908.  Rhamnus  Purshiana,  Comparative  Studies  of  the  Bark  with  Rhamnus 

Frangula,  by  A.  Tschirsch  and  J.  F.  A.  Pool.  Archiv.  Pharm., 
vol.  246,  pp.  315-25;  Chemical  Abstracts,  vol.  3,  p.  473. 

1909.  Cascara  Sagrada,  Cultivation  of,  by  R.  H.  True  and  G.  F.  Klugh. 

Proc.  Amer.  Pharm.  Assoc.,  vol.  57,  1909,  p.  824. 
1909.    Cascara  Sagrada,  Bitterless  Water  Soluble  Extract  of,  by  Dr.  M.  Pen- 
shuck.    Pharm.  Ztg.,  vol.  54,  1909,  p.  149;  Chemical  Abstracts,  vol. 
3,  p.  1796- 

1909.    Cascara  Sagrada,  Tasteless  Extract  of,   Patented  in  Germany,  by 

Dr.  Max  Penshuck.    Druggists'  Cir.,  April,  1909,  p.  183;  Chemical 

Abstracts,  vol.  5,  March,  191 1,  p.  973. 
1909.    Rhamnus  Purshiana,  Fluidextract  of,  by  L.  Krober.    Apoth.  Ztg., 

vol.  24,  1909,  pp.  307-308;  Proc.  Amer.  Pharm.  Assoc.,  vol.  57,  1909, 

p.  80. 

1909.    Rhamnus  Purshiana,  American  Medicinal  Barks,  by  Alice  Henkel. 

Bulletin  139,  Bureau  of  Plant  Industry,  U.  S.  Dept.  of  Agriculture. 
1909.    Cascara  Sagrada,  Fluidextract  of,  Use  of  Ammonia  in,  by  C.  Symes. 

Amer.  Jour,  of  Pharm.,  vol.  81,  October,  1909,  p.  490;  Trans.  Brit. 

Pharm.  Conf.  (Yearbook  of  Pharmacy),  1909,  pp.  319-20;  Proc. 

Amer.  Pharm.  Assoc.,  vol.  58,  1910,  p.  86. 
1909.    Cascara   Sagrada,   Yellow  Volatile   Constituent,  by  F.   H.  Alcock. 

Phar.  Jour,  and  Pharmacist,  Nov.  27,  1909,  p.  666;  Proc.  Amer. 

Pharm.  Assoc.,  vol.  58,  1910,  p.  218. 


Am.  Jour.  Pharm. ) 
September,  1914.  J 


Rhamnus  Purshiana. 


413 


1909.  Cascara  Sagrada,  Preparation  of  Bitterless  Extract  by  Use  of  Zinc 

Oxide.  Jour,  de  Pharm.  d'Anvers;  Pharm.  Ztg.,  vol.  54,  1909,  p. 
594;  Proc.  Amer.  Pharm.  Assoc.,  vol.  58,  1910,  p.  80. 

1910.  Rhamnus  Purshiana,  Characters  of  Identity  of  Fluidextract,  by  L. 

Kroeber.    Pharm.  Praxis,  1910,  No.  1 ;  Pharm.  Ztg.,  vol.  55,  1910, 
p.  376;  Z.  Oesterr.  Apoth.  Ver.,  vol.  49,  p.  16;  Proc.  Amer.  Pharm. 
Assoc.,  vol.  58,  1910,  p.  86;  Chemical  Abstracts,  vol.  5,  p.  2696. 
1910.    Cascara  Sagrada,  Bark  Introduced  in  1872  by  Donnelly,  by  J.  W. 

Forbes.  Practical  Druggist,  Aug.,  1910,  p.  48;  Chemical  Absts., 
vol.  5,  191 1,  p.  2696. 

1910.  Cascara  Sagrada,  Wine  Prepared  from  Bitterless  Fluidextract  of,  by 

Dr.  B.  Borner.    Apoth.  Ztg.,  vol.  25,  1910,  p.  591. 

191 1.  Cascara  Sagrada,  Aromatic  Fluidextract  of,  New  Formula  and  Proc- 

ess, by  R.  C.  Cowley.  Chem.  and  Drug.,  July  22,  191 1,  p.  46;  Proc. 
Amer.  Pharm.  Assoc.,  vol.  59,  191 1,  p.  59;  Chemical  Absts.,  vol. 
6,  p.  411. 

191 1.  Cascara  Sagrada,  Bitterless  Fluidglycerate,  by  G.  M.  Beringer.  Drug- 
gist Circular,  May,  191 1. 

191 1.  Cascara  Sagrada,  Bitterless  Extract  of,  Use  of  Zinc  Oxide.  Pacific 
Drug  Review,  Aug.,  191 1. 

191 1.  Cascara  Sagrada,  Preparation  of  Bitterless  Extract  and  Fluid- 
extract,  by  Dr.  B.  Borner.  Proc.  Amer.  Pharm.  Assoc.,  vol.  59, 
191 1,  p.  60. 

191 1.  Cascara  Sagrada,  Identification  by  Method  of  Pyro-analysis,  by  L. 

Rosenthaler.    Proc.  Amer.  Pharm.  Assoc.,  vol.  59,  191 1,  p.  149. 

1912.  Cascara  Sagrada,  Preparation  of  Fluidextract  of.    Apoth.  Ztg.,  vol. 

27,  PP-  32i~3i ;  Chemical  Absts.,  vol.  6,  p.  1953. 
1912.    Cascara  Sagrada,  Culture  of,  Pharmacal  Plants  and  their  Culture,  by 
Dr.  Albert  Schneider.    California  State  Board  of  Forestry,  Bul- 
letin 2,  pp.  42,  141. 

1912.    Cascara  Sagrada,  Perestaltin,  by  Tschirsch  and  Monikowski.  (Arch. 

der  Pharm.)    Druggists'  Cir.,  Sept.,  1912,  p.  517. 
1912.    Rhamnus  Purshiana,  The  Medullary  Ray  Cells  in,  by  Dr.  H.  Kraemer. 

Amer.  Jour,  of  Pharm.,  vol.  84,  1912,  p.  385;  Chemical  Absts.,  vol. 

6,  p.  3160. 

1912.  Cascara  Sagrada,  Apparatus  for  Estimation  of  the  Extract  of,  by 
E.  Biittner.  Sudd.  Apoth.  Ztg.,  vol.  52,  p.  271 ;  Chemical  Absts., 
vol.  6,  p.  1818. 

1912.  Cascara  Sagrada,  Preparation  of  Purified  Extract  of,  by  Diefenbach. 

Apoth.  Zeit.,  vol.  26,  p.  1046;  Chemical  Absts.,  vol.  6.  p.  913. 

1913.  Cascara  Sagrada,  Crude  Botanical  Drugs,  by  R.  H.  True.  Pharm. 

Era,  Jan.,  1913,  p.  9. 

1914.  Rhamnus  Purshiana  and  Rhamnus  Californica,  The  Medullary  Ray 

Cells  in,  by  Oliver  A.  Farwell.  Jour.  Amer.  Pharm.  Assoc.,  vol. 
3,  May,  19 14,  p.  649. 

University  of  Washington,  College  of  Pharmacy, 
Seattle,  Washington,  June  17,  1914. 


414  Insecticidal  Value  of  Larkspur  Seed.  {As™pteXerPi9iT' 

THE  INSECTICIDAL  VALUE  OF  FLUIDEXTRACT  OF 
LARKSPUR  SEED.* 

By  J.  B.  Williams. 

An  examination  of  several  samples  of  fluidextract  of  larkspur 
seed  on  the  market  at  the  present  time  showed  a  very  marked  dif- 
ference in  their  physical,  chemical,  and  insecticidal  properties.  The 
samples  examined  varied  in  color  from  a  dark  brown  to  a  very  light 
yellow ;  the  alcoholic  content  from  40  per  cent,  to  80  per  cent.,  the 
fixed  oil  content  from  less  than  0.2  per  cent,  to  nearly  20  per  cent., 
the  alkaloidal  strength  from  0.43  per  cent,  to  over  1  per  cent.,  while 
the  insecticidal  value  varied  500  per  cent.  (1  to  5). 

With  the  object  in  view  of  determining  if  possible  the  constit- 
uent of  larkspur  seed  to  which  it  owes  its  insecticidal  properties, 
and  the  best  means  of  extracting  the  same,  a  number  of  fluidextracts 
were  prepared,  using  various  menstrua.  The  resulting  fluidextracts 
were  assayed  for  alkaloidal  content  and  also  for  fixed  oil,  and  their 
insecticidal  value  was  determined  by  tests  on  living  insects  (bedbugs). 
The  seed  used  was  that  of  DeipJiiniuni  ajacis,  L.,  and  was  ground  to 
a  No.  30  powder.  The  methods  of  extraction  were  as  follows  : 

•No.  1. — Extracted  by  percolation  with  95  per  cent,  alcohol,  the 
strong  percolate  reserved  and  extraction  continued  until  the  drug  was 
practically  exhausted ;  the  weak  percolate  evaporated  to  a  soft  extract 
and  dissolved  in  the  reserved  portion,  and  sufficient  95  per  cent, 
alcohol  added  to  make  1  c.c.  for  each  gramme  of  drug  used.  Upon 
standing  this  fluid  separated  into  two  well-defined  layers,  the  upper 
oily  layer  equalling  about  45  per  cent,  and  the  lower  layer  about  55 
per  cent,  of  the  whole.  These  were  separated  and  each  made  up  to 
the  original  volume  with  95  per  cent,  alcohol  and,  for  purposes  of 
identification,  marked  i-A  for  the  upper  and  i-B  for  the  lower 
layer. 

No.  2. — Extracted  by  percolation  in  usual  manner  with  dilute 
alcohol. 

No.  3. — Extracted  with  30  per  cent,  alcohol. 

No.  4. — Extracted  with  petroleum  benzine,  the  benzine  removed 


*  Presented  at  the  meeting  of  the  American  Chemical  Society  at  Rochester, 
N.  Y.,  September,  1913. 


As™ptemberf i9iT' }    Insecticidal  Value  of  Larkspur  Seed.  415 

by  evaporation  on  the  water-bath  and  the  residue  dissolved  in  95  per 
cent,  alcohol. 

No.  5. — Extracted  with  petroleum  benzine,  the  benzine  solution 
shaken  out  with  dilute  acid  to  remove  the  greater  part  of  the  alkaloid, 
then  evaporated  and  the  residue  dissolved  in  95  per  cent,  alcohol. 

No.  6. — Extracted  with  10  per  cent  acetic  acid,  the  acid  removed 
by  distillation  and  the  residue  dissolved  in  dilute  alcohol. 

No.  7. — The  drug  residue  from  No.  6  extracted  with  95  per  cent 
alcohol. 

No.  8. — Extracted  with  95  per  cent,  alcohol  until  a  yield  of  1  c.c. 
for  each  gramme  of  drug  used  was  obtained.  This  gave  a  perfectly 
clear  fluid,  showing  no  signs  of  separating  after  standing  several 
weeks. 

No.  9. — The  extraction  of  drug  residue  of  No.  8  continued  until 
a  further  yield  of  1  c.c.  for  each  gramme  of  drug  used  was  obtained. 

No.  10. — The  alkaloidal  residues  of  several  assays  dissolved  in 
sufficient  95  per  cent,  alcohol  to  make  a  1  per  cent,  solution. 

These  fluidextracts  varied  in  color  from  a  dark  brown  (No.  6)  to 
a  very  light  yellow,  and  after  standing  several  weeks,  with  the  excep- 
tion of  Nos.  2,  3,  and  6,  which  show  some  sediment,  are  in  good 
condition. 

The  alkaloid  and  fixed  oil  contents  are  as  follows : 


Color  Alkaloid  Oil 

f  i— A  Pale  yellow  0.26  21.34 

\  i-B  Yellow  0.81  7.08 

2  Dark  brown          1.42  0.19 

3  Dark  brown          1.26  0.12 

4  Pale  yellow  0.17  30.37 

5  Pale  yellow  0.06  30.54 

6  Very  dark  brown  1.24  0.14 

7  Yellow  0.06  23.67 

8  Yellow  0.60  24.76 

9  Pale  yellow  0.11  3.60 

10  Reddish  yellow  1.0  (not  assayed) 


The  drug  itself  assayed  1.78  per  cent,  alkaloids  and  36.1  per  cent. 

oil. 

The  insecticidal  values  of  the  fluids  were  determined  by  Mr.  H. 
C.  Hamilton  by  the  method  of  Houghton  &  Hamilton.*  The  results 
were  as  follows : 

*  Eleventh  Report  of  the  Michigan  Academy  of  Science,  1909. 


416 


Progress  in  Pharmacy. 


J  Am.  Jour.  Pharm. 
)  September,  1914. 


Effective  dilution  Coefficient. 


U-B   .1-50  2.5 

2  1-18  0.9 

3  1-12  0.6 

4  1-120  .  6.0 

5  ...1-150  7.5 

6  1-18  0.9 

7    1-120  6.0 

8  i— 100  5.0 

9  1-15  0.75 

10  1-12  0.6 

11  standard...:  1-20  1.0 


From  the  above  results  it  would  appear  that  it  is  the  oil  and  not 
the  alkaloid  to  which  larkspur  seed  owes  its  insecticidal  properties, 
and,  since  the  fluid  is  seldom  used  internally  but  almost  exclusively 
as  an  insecticide,  it  would  seem  that  the  menstruum  that  will  extract 
the  largest  amount  of  oil  is  the  proper  one  to  use.  It  should  be  noted, 
however,  that  the  alkaloid  has  a  slight  insecticidal  value,  as  the  sample 
containing  i  per  cent,  of  alkaloid  and  no  oil  was  one-tenth  as  active  as 
the  samples  containing  a  high  content  of  oil. 

Analytical  and  Experimental  Department, 
Parke,  Davis  &  Co..  Detroit,  Mich. 


PROGRESS  IN  PHARMACY. 

A  Quarterly  Review  of  Some  of  the  More  Interesting  Litera- 
ture Relating  to  Pharmacy  and  Materia  Medica. 

By  M.  I.  Wilbert,  Washington,  D.  C. 

The  European  war  has  precipitated  a  condition  unprecedented 
and  unparalleled  in  the  history  of  the  drug  trade  of  this  country, 
and  has  demonstrated  as  no  other  line  of  argument  possibly  could 
that  we  in  America  are  still  largely  dependent  on  European  countries 
for  our  supplies  of  drugs  and  chemicals.  More  than  50  per  cent, 
of  the  drugs  and  chemicals  used  in  pharmacy  and  allied  industries 
has  been  subjected  to  marked  advances  in  price.  The  available 
stocks  of  many  articles  of  a  staple  nature  appear  to  have  been 
at  a  rather  low  level,  and  some  of  the  chemicals  of  German  origin 
are  already  practically  exhausted. 

It  will  no  doubt  be  months  before  the  drug  market  can  adjust 


Am.  Jour.  Pharru.  ) 
September,  1914.  J 


Progress  in  Pharmacy. 


417 


itself  to  the  suddenly  changed  conditions,  and  the  ultimate  solu- 
tion of  the  problems  that  are  now  presented  will  be  eagerly  awaited 
by  all.  The  influence  that  the  changed  conditions  will  have  on 
American  Pharmacy  should  be  a  beneficial  one,  as  the  present 
scarcity  of  articles  that  could  be  made  will  no  doubt  stimulate  the 
growth  of  chemical  industries  in  this  country. 

Considerable  concern  has  been  expressed  as  to  the  whereabouts 
of  the  German-American  apothecaries  and  their  friends  who  in 
their  trip  through  Europe  reached  Bremen  on  July  13.  They  were 
the  guests  of  the  Berlin  apothecaries  on  July  15,  16  and  17.  (Apoth- 
Ztg.j  1914,  vol.  29,  pp.  644-645,  657-658.)  An  elaborate  program 
had  been  prepared  for  their  entertainment,  one  day  being  spent  at 
the  pharmaceutical  institute  of  the  University  of  Berlin  at  Dahlen. 
The  apothecaries  of  Vienna,  Munich,  and  several  of  the  other  large 
cities  in  Germany,  Austria,  Switzerland,  and  France  had  also  pre- 
pared elaborate  programs  for  entertaining  the  American  pharmacists, 
but  their  itinerary  has  no  doubt  been  interrupted  by  the  general 
disturbance  on  the  continent. 

Friederich  Mohr. — On  June  21,  1914,  there  was  unveiled  in  the 
city  of  Coblentz,  Germany,  a  monument  to  one  of  the  pioneers  in 
pharmacy,  Friederich  Mohr,  who  despite  the  fact  that  he  was  the 
author  of  probably  the  original  text-book  on  the  practice  of  pharmacy 
is  perhaps  more  widely  known  for  his  connection  with  the  develop- 
ment of  analytical  chemistry  than  with  that  of  galenical  pharmacy. 
Pharmacists  of  an  older  generation  will  remember  the  book  "  Prac- 
tical Pharmacy  "  by  Mohr  and  Redwood,  an  American  edition  of 
which,  edited  by  Wm.  Procter,  Jr.,  was  in  its  day  generally  referred 
to  as  Mohr,  Redwood  and  Procter's  pharmacy.  Friederich  Mohr 
was  born  in  the  city  of  Coblentz  in  1806,  was  a  student  at  Bonn, 
Berlin,  and  Heidelberg,  a  voluminous  writer,  and  is  frequently  re- 
ferred to  as  the  classic  writer  of  pharmacy.  His  text-book  of 
pharmaceutical  technic  was  first  published  in  1847,  ms  text-book  on 
titration  methods  in  1855,  and  a  commentary  on  the  first  edition  of 
the  German  Pharmacopoeia  in  1874.  Most  of  his  life  was  spent  in 
the  pharmacy  left  him  by  his  father  and  it  was  not  until  he  reached 
his  sixtieth  year  that  he  was  called  as  a  professor  to  Bonn,  where 
he  died  in  1879. — Apoth.-Ztg.,  1914,  vol.  29,  pp.  547-550. 

Before  this  copy  of  the  Journal  reaches  its  readers  the  meetings 
of  the  National  Association  of  Retail  Druggists  and  the  American 
Pharmaceutical  Association  will  have  become  history.   From  present 


4i8 


Progress  in  Pharmacy. 


( Am.  Jour.  Pharm. 
\  September,  1914. 


indications  both  of  these  meetings  will  be  interesting,  profitable 
and  well  attended. 

The  American  Chemical  Society's  summer  or  fall  meeting,  which 
was  to  have  been  held  in  the  city  of  Montreal,  Canada,  September 
15th  to  1 8th,  has  been  indefinitely  postponed  because  of  the  European 
war  and  the  present  outlook  is  that  the  next  meeting  of  the  American 
Chemical  Society  will  be  held  in  New  Orleans,  April  ist  to  3d,  191 5. 

U.  S.  P.  Revision. — The  fourth  and  fifth  instalments  of  abstracts  - 
of  proposed  changes  with  new  standards  and  descriptions  for  the 
United  States  Pharmacopoeia,  ninth  revision,  have  been  published. 
The  first  includes  proposed  proximate  assays  of  crude  drugs  and 
galenical  preparations  and  the  latter  embraces  most  of  the  biological 
products  and  volatile  oils.  The  material  so  far  published  should 
prove  a  fruitful  source  for  discussion  at  the  Detroit  meeting  of  the 
American  Pharmaceutical  Association. 

Official  Assay  Processes. — Dichgans,  H.,  in  concluding  a  com- 
parative examination  of  pharmacopceial  methods  for  the  assay  of 
potent  drugs  and  medicinal  preparations,  states  that  his  results  in- 
dicate that  the  directions  for  alkaloidal  assay  included  in  many  of 
the  pharmacopoeias  are  not  at  all  suited  to  the  purpose.  The  results 
obtained  are  in  many  instances  variable,  while  in  others  the  methods 
are  so  complicated  that  they  are  unsuited  for  general  practice.  The 
different  methods  when  applied  to  the  same  material  give  widely 
variable  results,  indicating  that  uniformity  in  the  content  of  potent 
drugs  can  be  secured  only  when  the  method  of  assay  adopted  is 
uniform. 

Total  Extractive  as  a  Factor  in  Fluid  Extract  Manufacture. 
(Maines  and  Gardner.) — The  determination  of  total  extractive  is 
an  important  factor  in  the  manufacture  of  fluid  extracts,  especially 
those  of  the  known  alkaloidal  drugs.  A  table  of  the  total  extractive 
determinations  is  given  which  represents  estimations  covering  many 
years  of  work,  and  the  products  of  several  of  the  large  manufactures. 
— /.  Am.  Pharm.  Assoc.,  1914,  vol.  3,  pp.  997-1000. 

Useful  Drugs.  (Report  of  the  Board  of  Trustees.) — The  work 
of  the  committee  on  a  selected  list  of  drugs  has  resulted  in  the  publica- 
tion of  the  book  called  "  Useful  Drugs."  This  has  already  been 
adopted  as  a  text-book  by  a  number  of  our  best  schools ;  its  adoption 
has  been  considered  by  the  State  licensing  boards,  one  already  having 
adopted  it,  and  there  is  every  indication  that  this  enterprise  will  have 
a  most  beneficial  effect. — /.  Am.  M.  Assoc.,  1914,  vol.  63,  p.  75. 


AseFtembrerPi9iT" }  Progress  in  Pharmacy.  419 

Prescriptions.  (Taylor,  George  B.) — A  rep'ort  on  carelessness 
in  the  filling  of  simple  prescriptions  in  the  State  of  Louisiana.  In 
December,  191 3,  a  prescription  calling  for  2  gm.  of  boric  acid  and  2 
ounces  of  distilled  water  was  filled  by  68  New  Orleans  druggists. 
Of  these,  22,  or  32.3  per  cent.,  were  correct  both  as  to  distilled  water 
and  to  weight  (some  allowance  is  given  in  weight)  ;  17,  or  25  per 
cent.,  were  correct  as  to  weight  but  not  as  to  the  use  of  distilled 
water;  14,  or  20.6  per  cent.,  were  correct  as  to  distilled  water  but 
incorrect  in  weight;  and  15,  or  22.1  per  cent.,  were  incorrect  both 
as  to  use  of  distilled  water  and  as  to  weight. — Rep.  Louisiana  Bd. 
H.,  1912,  1913,  pp.  176-187. 

Weights  and  Measures. — In  an  address  before  the  National  Con- 
ference on  Weight  and  Measures  of  Washington,  D.  C,  Mr.  F.  P. 
Downing,  chief  inspector  of  weights  and  measures  for  the  State  of 
Wisconsin,  referred  to  alleged  inaccuracies  in  the  delicate  weighing 
apparatus  in  drug  stores,  jewelry  stores,  and  the  like.  Coin  weights 
used  on  such  scales  were  stated  by  him  to  be  often  10  to  30  per  cent, 
light.  In  a  recent  inspection  of  drug  stores  in  Milwaukee  22.1  per 
cent,  of  the  dispensing  scales  and  43.6  per  cent,  of  the  dispensing 
weights  in  use  were  found  in  error. — Pharm.  J.,  1914,  vol.  92,  p.  905. 

Food  and  Drugs  Law. — An  important  interpretation  of  the  pure 
food  and  drugs  act  was  handed  down  on  June  13,  by  the  United 
States  Circuit  Court  of  Appeals  at  Cincinnati  in  the  case  of  the 
United  States  vs.  Forty  Barrels  and  Twenty  Kegs  of  coca  cola, 
which  reads  in  part  as  follows :  The  general  purpose  and  intent  must 
be  deemed  to  be  the  prevention  of  fraud  and  deception,  so  that  the 
purchaser  can  get  the  thing  he  has  a  right  to  suppose  he  is  getting, 
rather  than  the  protection  of  the  public  health  to  the  extent  of  pre- 
venting the  purchaser  from  deliberately  and  intentionally  buying  a 
particular  food  which  is  what  it  purports  to  be,  even  though  a  jury 
might  think  it  "  deleterious. " — Druggists'  Circular,  1914,  vol.  58, 
p.  487. 

The  Patent  Medicine  Business.  (News  Note.) — Dr.  S.  S.  Gold- 
water,  commissioner  of  health  of  New  York  City,  has  announced 
that  a  systematic  investigation  of  the  patent  medicine  business  would 
be  begun  at  once.  It  is  proposed  to  insist  that  the  manufacturer  of 
a  patent  medicine  name  the  ingredients  in  the  mixture  and  it  is  be- 
lieved that  public  opinion  is  sufficiently  enlightened  to  support  this 
movement. — /.  Am.  M.  Assoc.,  1914,  vol.  63,  p.  411.  See  also  Drug- 
gists' Circular,  191 4,  vol.  58,  p.  481. 


420 


Progress  in  Pharmacy. 


( Am.  Jour.  Pharm. 

t  September,  1914. 


Patent  Medicines.  {Anon.) — -Our  Parliamentary  correspondent 
learns  that  a  further  prolonged  sitting  of  the  Select  Committee  on 
Patent  and  Proprietary  Medicines  was  held  on  Tuesday  at  the  House 
of  Commons.  Sir  Henry  Norman,  the  Chairman,  again  presided. 
Altogether,  the  meeting  lasted  for  some  hours,  and,  as  the  result, 
about  one-half  of  the  draft  report  has  now  been  disposed  of. — Chem. 
and  Drug.,  1914,  vol.  85,  p.  223. 

Consumption  Cure.  (Editorial.) — After  a  hearing  extending 
over  seven  days,  the  libel  action  against  the  British  Medical  Associa- 
tion brought  by  Mr.  C.  H.  Stevens,  the  proprietor  of  "  Stevens' 
Consumption  Cure,"  has  terminated  in  a  verdict  for  the  defendants. 
The  jury,  after  an  absence  of  about  10  minutes,  found  the  matter 
complained  of  was  of  the  nature  of  fair  comment  and  judgment  was 
accordingly  given  in  favor  of  the  British  Medical  Association. — 
Pharm.  J.,  1914,  vol.  93,  p.  191. 

Proprietary  Remedies.  (Editorial.) — The  drug  fund  of  the 
London  Insurance  Committee  is  threatened  by  the  over-prescribing 
of  proprietaries  and  the  drugs  and  appliances  sub-committee  of  the 
Insurance  Committee  has  issued  a  list  of  articles  as  not  being 
"  proper  and  sufficient  drugs  and  medicines  and  prescribed  ap- 
pliances required  to  be  provided  for  insured  persons,"  under  the 
National  Insurance  Act. — Chem.  and  Drug.,  1914,  vol.  85,  p.  221. 

National  Insurance  Pharmacopoeia. — kt  Karshish  "  suggests  the 
adoption  of  a  national  insurance  pharmacopoeia  to  avoid  unnecessary 
deficiencies  in  the  drug  fund. — Pharm.  J.,  1914,  vol.  93,  p.  11. 

British  Pharmacopoeia.  (London  Letter.) — The  work  of  prepar- 
ing a  new  edition  of  the  British  Pharmacopoeia  has  now  been  com- 
pleted. One  of  the  chief  features  will  be  that  limits  of  impurity  in 
drugs  and  medicinal  chemicals — especially  dangerous  impurity — 
will  be  carefully  defined.  Another  feature  of  the  book  is  an  ex- 
tension of  chemical  standardization  to  drugs  not  at  present  standard- 
ized, but  there  is  no  recognition  of  physiologic  standardization. 
The  international  unification  of  the  quality  of  preparations  of  potent 
drugs,  which  has  received  the  endorsement  of  various  nations,  has  due 
recognition  in  the  forthcoming  book. — /.  Am.  M.  Assoc.,  1914,  vol. 
62,  p.  2039. 

British  Pharmacopoeia.  (Editorial.) — At  its  meeting  on  July  13 
the  Executive  Committee  of  the  General  Medical  Council  formally 
adopted  the  completed  draft  of  the  British  Pharmacopoeia,  1914,  as 
submitted  by  the  Pharmacopoeia  Committee.    It  was  resolved  that 


Am.  Jour.  Pharm.  ) 
September,  1914.  j 


Progress  in  Pharmacy. 


421 


copies  in  advance  of  publication  should  be  made  accessible  to  the 
public  for  inspection  at  the  offices  of  the  Council  in  London,  Edin- 
burgh, and  Dublin  on  Monday,  August  10.  The  official  publication 
of  the  Pharmacopceia  will  be  made  in  the  London  Gazette  on  Friday, 
October  9,  on  which  day  copies  will  be  on  sale  at  the  publishers. — 
Pharm.  J.,  1914,  vol.  93,  p.  78. 

British  Pharmaceutical  Conference. — The  51st  annual  meeting 
of  the  British  Pharmaceutical  Conference  was  held  at  Chester,  July 
20  to  25,  1914,  presided  over  by  Edward  H.  Farr,  who  chose  for 
the  subject  of  his  presidential  address  a  discussion  of  recent  work 
on  plant  products.  The  proceedings  are  reported  at  length  in  the 
British  pharmaceutical  journals  for  July  25,  1914,  and  the  papers 
presented  are  published  in  the  journals  of  the  same  date.  The  total 
number  of  papers  presented  was  28,  of  which  25  were  read  in  the  or- 
dinary section  and  3  in  the  practice  section.  The  nature  of  these 
communications  was  well  up  to  the  average  and  should  prove  to  be  of 
interest  to  all  who  are  in  any  way  engaged  in  the  practical  side  of 
their  profession. — Pharm.  1914,  vol.  93,  pp.  1 17-139;  also  Chem. 
and  Drug.,  1914,  vol.  85,  pp.  161-195. 

The  papers  read  in  the  ordinary  section  of  the  British  Pharma- 
ceutical Conference  included  the  following: 

Estimation  of  Strychnine  in  the  Presence  of  Brucine.  (Ditt, 
D.  B.) — A  modification  of  Gordon's  process  is  recommended,  the 
experimental  data  recorded  showing  that  the  use  of  1  c.c.  of  con- 
centrated nitric  acid  for  each  0.25  Gm.  of  brucine  in  the  propor- 
tion of  1  to  10  volumes  of  acid  solution,  made  for  a  period  of  20 
minutes  at  ordinary  temperature,  is  quite  sufficient  to  destroy  all 
the  brucine. — Pharm.  J .,  191 4,  vol.  93,  p.  120. 

The  Purity  of  Pepsin  Bacteriologically  Considered.  (Quant 
Ernest.) — A  report  on  11  samples  of  pepsin  from  various  sources, 
only  two  of  which  were  free  from  micro-organisms.  The  author 
suggests  that  the  product  may  be  improved  by  the  presence  of  free 
acid  and  the  use  of  chloroform. — Pharm  L,  1914,  vol.  93,  pp.  120,  121. 

The  Adulteration  of  Belladonna  Leaves.  (Allen  and  Deane.)  — 
The  leaves  of  Phytolacca  decandra,  Scopola  carniolica,  and  Ailan- 
thus  glandulosa  were  found  admixed  with  commercial  belladonna 
from  Continental  sources  to  the  extent  of  from  20  to  80  per  cent. 
The  authors  review  the  literature  and  present  a  number  of  illustra- 
tions showing  the  macroscopic  and  microscopic  features  of  the 


422 


Progress  in  Pharmacy. 


f  Am.  Jour.  l'harm. 
1  September,  1914. 


several  substitutes  compared  with  the  distinguishing  features  of 
the  genuine  drug. — Pharm.  J.}  1914,  vol.  93,  pp.  121-123. 

The  Rate  of  Dialysis  of  Alkaloids  in  Aqueous  Solution  and 
in  the  Form  of  Galenicals.  (Finnemore,  H.) — From  experiments 
reported  the  author  'concludes  that  strychnine  in  aqueous  solution 
diffuses  more  rapidly  than  in  the  form  of  the  liquid  extract  of  nux 
vomica,  and  this  fact  may  have  some  bearing  on  the  therapeutic 
effect  of  the  two. — Pharm.  J.,  1914,  vol.  93,  pp.  123,  124. 

The  Incompatibility  of  Strychnine  and  Nux  Vomica  with  Alka- 
lies, Iodides,  and  Bromides.  (Finnemore  and  Williamson.) — The 
most  striking  feature  of  the  experiments  now  recorded  is  the  dif- 
ference in  the  behavior  towards  alkalies  of  strychnine  in  the  form 
of  the  solution  and  that  existing  in  its  natural  state  in  admixture 
or  combination  with  the  other  ingredients  of  nux  vomica  seeds. 
It  appears  that,  whereas  strychnine  and  alkalies  or  iodides  may 
become  dangerous  under  varied  and  indeterminate  conditions,  when 
the  drug  is  given  in  the  form  of  the  tincture  or  the  liquid  extract 
no  precipitation  occurs  and  no  danger  need  be  apprehended,  pro- 
vided the  concentration  is  not  greater  than  that  found  under  normal 
conditions  of  prescribing  and  dosage. 

The  Analytical  Characters  of  Benzoin.  (Cocking  and  Kettle.)  — 
The  alcohol  soluble  matter  in  benzoin  is  not  readily  determined 
directly,  owing  to  the  volatility  of  the  balsamic  constituents,  and  the 
easiest  way  is  to  obtain  it  by  exhausting  the  drug  by  alcohol.  A 
modified  method  for  the  determination  of  the  aromatic  acid  is  sug- 
gested, and  a  table  showing  the  composition  of  a  number  of  the 
commercial  samples  of  the  drug  is  included  with  the  paper. — Pharm. 
J..  1914,  vol.  93,  pp.  125,  126. 

The  Mineral  Constituents  of  Certain  Tinctures  and  Drugs. 
(Lewis,  S.  Judd. ) — The  molecular  structure  of  chlorophyll  is  very 
closely  related  to  haematin,  the  red  coloring  matter  of  the  blood. 
The  former,  under  the  influence  of  -light,  brings  about  the  absorp- 
tion of  carbon  dioxide  by  plants  and  the  elimination  of  oxygen, 
and  has  magnesium  as  an  essential  element,  hence  magnesium  is 
to  be  anticipated  in  all  mineral  matter  which  has  passed  through 
the  vegetable  cell.  The  presence  of  iron  is  also  necessary  for  the 
formation  of  chlorophyll,  although  it  does  not  enter  into  the  con- 
stituents of  the  pigment.  Potassium  and  calcium  are  also  con- 
stantly present,  and  the  occurrence  of  other  metals  is  frequently 
more  or  less  accidental.    Sodium  is  widely  distributed,  while  lithium, 


Am.  Jour.  Pharm.  ) 
September,  1914.  / 


Progress  in  Pharmacy.. 


423 


aluminum  and  manganese  are  rarely  encountered.  Copper  is  not  rare. 
Among  the  non-metals,  sulphur  and  phosphorus  are  nearly  always 
present  in  the  ashes  of  plants. — Pharm.  J.,  1914,  vol.  93,  pp.  126-128. 

The  Stability  of  Cinnamic  Aldehyde.  (Phillips,  H.  Adie.)  — 
It  has  been  contended  that  in  the  distillation  of  the  oil  from  chips 
there  was  a  likelihood  that  some  of  the  cinnamic  aldehyde  was 
oxidized  to  cinnamic  acid.  The  experiments  reported  seem  to  prove 
that  under  the  usual  conditions  prevailing  under  steam  distillation 
cinnamic  aldehyde,  both  pure  and  as  a  constituent  of  cinnamon  oil, 
is  not  appreciably  oxidized. — Pharm.  J.,  1914,  vol.  93,  pp.  129,  130. 

The  Composition  of  Tinctura  Iodi  Decolorata.  (Pratt,  Walter 
R.) — The  finished  tincture  made  according  to  the  directions  of  the 
British  Pharmaceutical  Codex  is  an  alcoholic  solution  of  ammonium 
iodide,  with  excess  of  ammonia  containing  about  0.1  per  cent, 
iodoform  and  in  some  cases  ammonium  iodate,  hydroxylamine,  and 
acetaldehyde. — Pharm.  J.,  1914,  vol.  93,  pp.  130,  131. 

The  Determination  of  Iron  in  the  Presence  of  Phosphoric  Acid. 
(Corfield  and  Pratt.) — The  gravimetric  determination  of  ferric  iron 
in  the  presence  of  even  small  quantities  of  phosphates  gave  results 
which  are  much  too  high  and  are  variable  among  themselves.  Both 
the  idiometric  and  reduction  by  stannous  chloride  volumetric  meth- 
ods give  results  which  are  very  accurate  and  can  be  equally  well 
used  in  the  presence  of  phosphoric  acid.  The  former  method  gives 
results  which  tend  to  be  somewhat  high. — Pharm.  J.,  igi4,  vol. 
93.  PP-  I3T-I33- 

An  Improved  M ethod  for  the  Administration  of  Extr actum  Filicis 
Maris  Liqnidum.  (Crossley,  Holland  F.  W.) — Oleoresin  of  as- 
pidium  can  best  be  exhibited  in  the  form  of  a  jelly  made  with  gelatin 
and  glycerin,  sweetened  with  saccharin  and  flavored  with  oil  of  cin- 
namon. This  form  of  preparation  is  said  to  be  more  palatable  than 
emulsions  or  capsules,  and  the  bulk  is  reasonable  in  relation  to  the 
dose. — Pharm.  J.,  1914,  vol.  93,  p.  133. 

The  place  of  Carbon  Bisulphide  in  Official  Pharmacy  and  Sug- 
gestion for  its  Further  Use.  (Alcock,  F.  H.) — The  use  of  carbon 
disulphide  is  recommended  as  a  solvent  for  fats  and  as  a  means  for 
ascertaining  the  amount  of  constituents  extractable  from  official  liquid 
preparations,  such  as  liquid  extracts  and  tinctures.  Some  useful 
results  have  been  obtained,  a  number  of  which  are  recorded. — 
Pharm.  ./.,  1914,  vol.  93,  pp.  133,  134. 

The  Composition  of  the  Glycerophosphates  of  Commerce.  (Um- 


424 


Progress  in  Pharmacy. 


f  Am.  Jour.  Pharm. 
\  September,  1914. 


ney  and  Bennett.) — Calcium  glycerophosphate  is  of  variable  com- 
position and  does  not  contain  a  definite  proportion  of  water.  Potas- 
sium glycerophosphate  is  not  readily  obtainable  in  a  crystalline  form, 
and  the  crystalline  form  of  sodium  glycerophosphate  contains  5 
molecules  of  water.  Magnesium  glycerophosphate  is  rendered  more 
soluble  by  the  presence  of  citric  acid,  and  no  definite  formula  for 
the  hydrated  salts  can  be  given.  Ferric  glycerophosphate  should 
contain  approximately  15  per  cent,  of  metallic  iron  and  should  be 
completely  soluble  in  two  parts  of  water.— Pharm.  /.,  1914,  vol.  93, 
PP-  134.  135- 

Commercial  Standards  for  Dried  Magnesium  Sulphate,  Sodium 
Sulphate,  and  Sodium  Phosphate.  (Umney  and  Bennett.) — A  rea- 
sonable standard  for  dried  magnesium  sulphate  would  be  that  it 
should  be  prepared  by  drying  at  ioo°  until  it  has  lost  about  one-third 
of  its  weight,  and  that  the  product  should  contain  not  less  than  23 
per  cent,  and  not  more  than  31  per  cent,  of  water.  It  should  be  com- 
pletely and  readily  soluble  in  water.  Sodium  sulphate  should  be 
practically  anhydrous  and  should  not  contain  more  than  5  per  cent, 
of  water.  For  sodium  phosphate  5  per  cent,  of  water  would  be  a 
reasonable  limit. — Pharm.  J.,  1914,  vol.  93,  pp.  135,  136. 

Liquor  Opii  Sedativus.  (Bennett  and  Cocking.) — Suggestions 
to  improve  the  formula  included  in  the  British  Pharmaceutical 
Codex.  The  opium  should  be  exhausted  by  cold  maceration  in  lime 
water,  and  the  solution  should  be  subsequently  but  slightly  acidified 
by  hydrochloric  acid  or  sulphuric  acid,  after  the  addition  of  alcohol 
and  wine. — Pharm.  J.,  1914,  vol.  93,  pp.  136,  137. 

Some  Uses  of  a  Tincture  Press.  (Pollard,  E.  W.) — An  illus- 
trated description  of  possible  uses  of  a  tincture  press  as  a  pill-piper 
or  as  a  suppository  machine. — Pharm.  J.,  1914,  vol.  93,  pp.  137,  138. 

Anccsthetic  Ether  of  Commerce.  (Finnemore,  H.) — -An  exami- 
nation of  a  number  of  samples  of  ether  in  actual  use  shows  that, 
while  some  samples  may  have  been  rather  inferior,  in  the  main  they 
have  reached  a  fair  average  of  purity.  The  impurities  found  consist 
of  acetone,  water,  alcohol,  acetaldehyde,  peroxides,  and  acids. — 
Pharm.  J.,  1914,  vol.  93,  pp.  138,  139. 

Medical  Museum.  (Anon.) — The  Wellcome  Historical  Medi- 
cal Museum  in  London  was  reopened  on  May  28,  19 14,  in  a  per- 
manent home,  54  A,  Wigmore  Street,  Cavendish  Square,  London, 
W.  The  museum  is  open  daily  from  10  a.m.  to  6  p.m.,  Saturdays 
to  T  p.m.    Members  of  the  medical  profession  and  related  callings 


^pteXerfmT-}  Progress  in  Pharmacy.  425 

are  admitted  on  the  presentation  of  their  visiting  cards. — Sudd. 
Apoth.-Ztg.,  1914,  vol.  54,  p.  403. 

The  Hague  Opium  Conference. — The  third  conference  of  rep- 
resentatives of  the  Powers  for  the  purpose  of  regulating  the  produc- 
tion and  distribution  of  opium,  morphine,  and  cocaine  and  their 
derivatives  was  held  at  The  Hague,  June  23  to  25,  19 14.  It  was  con- 
cluded to  be  possible  to  put  the  convention  into  force  notwithstanding 
the  fact  that  some  Powers  have  as  yet  not  signed  the  convention  in 
compliance  with  Article  23. — Oil,  Paint  and  Drug  Rep.,  1914,  vol. 
86,  July  20,  p.  18. 

Opium  Suppression.  (Editorial.) — The  difficulty  of  inducing  an 
Oriental  nation  to  do  without  some  narcotic,  and  the  danger  of  opium 
smoking  being  superseded  by  the  still  worse  habits  of  cocaine  and 
morphine  injection,  have  long  been  noted.  In  the  course  of  a  recent 
trial  it  was  stated  that  during  the  past  two  months  about  200  pounds 
of  morphine  had  been  seized  by  the  customs  officials  at  Shanghai. — 
Pharm.  J.,  1914,  vol.  93,  p.  78. 

Opium  Habit. — In  answer  to  an  inquiry  the  Secretary  of  State 
for  the  Colonies  admits  that  it  is  the  fact  that  the  consumption  of 
fermented  liquors,  especially  beer  and  stout,  had  considerably  in- 
creased in  the  Malay  States  since  1909,  and  the  working  of  the  Excise 
Enactments  is  being  carefully  studied  with  a  view  to  the  proper  con- 
trol of  this  consumption. — Pharm  J.,  1914,  vol.  93,  p.  50. 

The  Harrison  Anti-narcotic  Bill  was  finally  agreed  to  by  the 
Senate  on  the  afternoon  of  Saturday,  August  15,  in  a  form  that  will 
undoubtedly  make  it  acceptable  to  members  of  the  House  and  to 
the  President. 

Smoking  Opium. — In  May  last  the  Commissioner  of  Internal 
Revenue  made  a  decision  regarding  aqueous  extract  of  opium,  in 
which  it  was  stated  that,  while  this  product  may  have  some  medicinal 
uses,  such  uses  may  be  covered  by  the  use  of  powdered  extract  of 
opium ;  also  it  is  stated  that  the  aqueous  extract  of  opium  is  used  to 
a  considerable  extent  by  opium  smokers  and  is  suitable  for  that  pur- 
pose. Under  the  decision,  the  manufacturers  of  this  product  are 
required  to  comply  with  the  law  as  to  smoking  opium.  Taking  up 
this  subject,  the  Treasury  Department  has  issued  a  decision  calling 
attention  to  the  action  of  the  Commissioner  of  Internal  Revenue, 
and  stating  that  this  product  is  within  the  scope  of  the  smoking 
opium  Jaw  passed  on  January  17,  1914,  which  prohibits  the  impor- 
tation of  such  opium,  and  the  collectors  of  customs  are  required  to 


426 


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I   September,  1914. 


refuse  delivery  of  aqueous  extract  of  opium  and  to  return  the  impor- 
tation to  the  country  whence  it  came. — Druggists'  Circular,  1914, 
vol.  158,  p.  487. 

Boylan  Law.  (A  News  Note.) — After  an  unavoidable  delay  in 
printing  them,  due  to  the  failure  of  the  State  Legislature  to  make 
an  appropriation  therefor,  the  Boylan  law  order  blanks,  which  must 
now  be  used  by  all  pharmacists,  druggists,  physicians,  dentists,  and 
veterinarians  in  New  York  State,  when  buying  opium  and  chloral, 
their  derivatives  and  preparations  containing  the  same,  are  now 
being  distributed. — Oil,  Paint  and  Drug  Rep.,  19 14,  vol.  86,  July  6, 
p.  11. 

Death  by  Poisoning  in  Great  Britain. — The  75th  annual  report  of 
the  Registrar-General  of  Births,  Deaths,  and  Marriages  in  England 
and  Wales  shows  that  the  number  of  deaths  due  to  poisons  and 
poisonous  substances  in  1912  was  neither  materially  larger  nor 
smaller  than  the  average  for  recent  years.  The  number  of  deaths 
certified  as  due  to  accidental  poisoning  by  scheduled  poisons  was 
122,  against  124  in  191 1,  and  by  non-scheduled  substances  102,  against 
115  in  191 1.  The  number  of  cases  in  which  poisons  were  taken  by 
suicides  was  547  (347  scheduled  and  200  non-scheduled)  ;  in  the 
previous  year  scheduled  poisons  were  used  in  324  cases,  and  non- 
scheduled  in  195. — Phar.  J.,  1914,  vol.  93,  p.  3. 

Responsibility  for  Poisoning.  (Anon.)- — The  responsibility  for  a 
fatal  and  an  additional  serious  case  of  poisoning  by  impure  barium 
sulphate,  used  in  the  course  of  a  Rontgen-ray  examination  at  Prague, 
has  finally  been  fixed  by  the  upper  court  at  Vienna.  This  court  decided 
that  the  pharmacist  in  charge  of  the  pharmacy  was  responsible  and 
guilty  of  neglect  because  of  his  having  failed  to  carefully  examine 
the  barium  sulphate  before  allowing  it  to  be  dispensed  or  used.  The 
assistants  in  the  pharmacy  and  in  the  wholesale  drug  establishment 
from  which  the  barium  sulphate  had  been  purchased  were  freed, 
despite  the  objection  made  by  the  State's  Attorney. — Siidd.  Apoth- 
Ztg.,  1914,  vol.  54,  p.  403. 

Studies  on  the  Absorption  of  Drugs.  (Hatcher  and  Eggleston.)  — 
A  summary  of  observations  on  the  absorption  of  drugs,  with  the  con- 
clusion that  the  ratio  of  absorption  from  the  four  common  channels 
of  administration  differs  for  each  drug.  No  rule  can  be  formulated 
for  the  calculation  of  the  appropriate  dose  by  one  mode  of  admin- 
istration from  the  dose  by  any  other  mode  of  administration.  Such 


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427 


determination  can  be  made  only  by  experiment. — /.  Am.  M.  Assoc., 
1914,  vol.  63,  pp.  469-473- 

Algocratine. — Mannich  and  Leemhuis,  from  the  pharmaceutical 
laboratory  of  the  University  of  Gottingen,  report  an  examination 
of  a  powder  offered  as  an  infallible  remedy  for  migraine,  neuralgia, 
grippe,  influenza,  and  other  diseases.  The  preparation  was  found 
to  consist  essentially  of  a  mixture  of  50  Gm.  phenacetin,  caffeine  10 
Gm.j  and  pyramidon  40  Gm.  The  claims  made  for  the  composition 
of  the  preparation  were  found  to  be  quite  untrue. — Apoth.-Ztg., 
1914,  vol.  29,  p.  553. 

Antimeningitis  Serum.  (Auer,  John.) — It  is  an  established  fact 
that  the  administration  of  antimeningitic  serum  by  intraspinal  injec- 
tion has  practically  turned  the  former  70  per  cent,  mortality  from 
epidemic  meningitis  into  70  per  cent,  recoveries.  Accumulated  ex- 
perience, however,  has  apparently  shown  that  the  injection  of  the 
serum  itself  may  have  been  the  cause  of  death  in  a  very  small  num- 
ber of  cases.  S.  P.  Kramer  holds  that  they  were  caused  by  tri- 
kresol  which  had  been  added  as  a  preservative  to  the  serum,  a  con- 
tention which  has  recently  been  supported  by  Hale  on  the  basis  of  ex- 
perimental work  on  dogs  and  cats. — /.  Am.  M.  Assoc.,  1914,  vol.  62, 
p.  1799. 

Transformation  of  Barbaloin  into  Beta-barbaloin.  ( Leger,  E.)  — 
When  barbaloin  is  kept  for  some  time  near  its  melting-point,  it 
becomes  converted  into  its  amorphous  isomer,  beta-barbaloin,  which 
accompanies  barbaloin  in  Cape  and  Socotrine  aloes.  The  action  of 
acetic  anhydride  on  barbaloin  at  ioo°  to  no°  also  brings  about  the 
same  change. —  (Compt.  rend.,  1914,  vol.  158,  p.  1903.)  Pharm.  J., 
1914,  vol.  93,  p.  83. 

Bichloride  Tablets.  (Vanderkleed  and  E'we.) — "Bichloride" 
antiseptic  tablet  with  tartar  emetic  administered  to  a  dog  produced 
profuse  vomiting  in  seven  minutes.  During  this  time,  however,  a 
sufficient  amount  of  the  bichloride  had  been  absorbed  to  cause  the 
death  of  the  dog  in  6J/2  hours.  This  experiment  indicates  that  to 
be  effective  the  emetic  must  act  more  promptly  than  it  did  in  this 
instance,  as  the  absorption  of  bichloride  takes  place  apparently  very 
rapidly. — Druggists'  Circular,  19 14,  vol.  58,  p.  465. 

Calcium  Therapy  of  Tuberculosis.  (Kahn,  M.) — In  looking 
over  the  mass  of  literature  relating  to  the  use  of  calcium  in  tuber- 
culosis one  is  left  in  doubt  whether  the  use  of  lime  in  the  treatment 
of  tuberculosis  is  to  be  recommended.   There  is,  however,  no  danger 


428 


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\  September,  1914. 


in  its  use,  and,  according  to  the  observations  of  a  number  of  phy- 
sicians, it  is  of  marked  benefit. —  {Med.  Rec,  1914,  vol.  85,  No.  21.) 
/.  Am.  M.  Assoc.,  1914,  vol.  62,  p.  1844. 

The  Determination  of  Camphor  in  Tablets  and  Pills.  (Dowzard, 
Edwin.) — Camphor  may  be  rapidly  and  completely  removed  from 
tablets  and  pills  by  distillation  in  a  current  of  steam.  The  watery 
distillate  contains  both  dissolved  and  undissolved  camphor,  which 
can  be  extracted  with  benzol.  By  determining  the  optical  rotation 
of  the  benzol  solution  the  amount  of  camphor  present  in  the  tablets 
or  pills  can  be  readily  calculated. — /.  Ind.  Eng.  Chem.,  1914,  vol. 
6,  pp.  489-490. 

Cerolin  (not  Creolin  as  printed  in  the  June  issue  of  this  Journal, 
p.  279)  consists  of  the  glycerides  of  fatty  acids  along  with  cho- 
lesterins,  lecithin,  and  ethereal  oil,  all  of  which  are  found  in  yeast. 
It  is  prepared  by  extracting  fresh  purified  beer  yeast  with  alcohol 
and  separating  the  dissolved  fat  from  the  alcoholic  extract  by  suit- 
able means.  Cerolin  is  said  to  be  useful  in  furunculosis,  acne,  sycosis, 
and  similar  affections  of  the  skin.  It  is  also  said  to  be  useful  in 
habitual  constipation,  leucorrhcea,  erosions  of  the  vagina  and  cervix, 
and  similar  diseases. — /.  Am.  M.  Assoc.,  19 14,  vol.  62,  p.  931. 

Cymarin. — Wiesel  considers  cymarin  a  valuable  supplement  to 
digitalis  because  of  the  rapidity  of  its  action. — Therap.  Monatsh., 
19T4,  vol.  28,  p.  508. 

Eisenzucker.  (Anon.) — Eisenzucker,  or  saccharated  ferric 
oxide,  is  official  in  several  pharmacopoeias,  but  not  in  the  United 
States  Pharmacopoeia.  It  consists  of  a  ferric  hydroxide  made 
soluble  by  the  addition  of  sugar  and  a  small  amount  of  sodium  hy- 
droxide. It  is  said  to  be  an  efficient  ferruginous  preparation.  The 
adult  dose  is  0.6  Gm.,  or  10  grains.  This  may  be  dissolved  in  equal 
parts  of  water  and  syrup. — /.  Am.  M.  Assoc.,  1914,  vol.  63,  p.  421. 

Electrargol.  (Puckner,  W.  A.) — Electrargol  is  a  colloidal  solu- 
tion of  silver  containing  a  small  percentage  of  sodium  arabate.  It 
contains  silver  equivalent  to  0.25  per  cent,  metallic  silver  (Ag). 
Electrargol  is  an  odorless,  tasteless  liquid,  appearing  transparent  and 
reddish-brown  by  transmitted  light  and  opaque  and  gray  by  reflected 
light.  The  addition  of  potassium  cyanide  solution  or  of  strong  nitric 
acid  yields  a  white  turbidity  on  the  addition  of  chlorides — 7.  Am.  M. 
Assoc.,  1914,  vol.  62,  p.  1808. 

Friedmann  Remedy. — A  number  of  clinicians  and  bacteriologists 
are  beginning  to  report  their  experiences  with  the  Friedmann  remedy. 


Am.  Jour.  Pharm.  \ 
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Progress  in  Pharmacy. 


429 


From  the  available  reports  it  would  appear  that  this  remedy  should 
not  be  used  under  any  conditions  until  such  time  as  a  sufficient  guar- 
anty can  be  offered  that  the  contaminations  and  pathogenic  organisms 
present  have  been  eliminated. — Therap.  Monatsh.,  1914,  vol.  28,  pp. 
509-511.   See  also  /.  Am.  M.  Assoc.,  1914,  vol.  63,  p.  177  and  p.  358. 

Galegine  Sulphate. — The  new  base  recently  discovered  and  iso- 
lated by  Tanret  from  Galega  officinalis,  the  common  goat's  rue, 
is  toxic  when  administered  by  hypodermic  or  intravenous  injection, 
both  for  cold-blooded  and  warm-blooded  animals. —  (Compt.  rend., 
1914,  vol.  159,  No.  108.)    Pharm.  J.,  1914,  vol.  93,  p.  195. 

Gitalin.  (Rosenthaler,  L.) — Report  of  experiments  which  tend 
to  confirm  the  assertion  made  by  Kiliani  that  gitalin  is  not  a  definite 
substance. — Schzveiz.  Apoth.-Ztg.,  1914,  vol.  52,  pp.  349,  350. 

Glyco-Heroin,  Smith.  (Puckner,  W.  A.)- — The  report  of  the 
Council  on  Pharmacy  and  Chemistry  of  the  American  Medical  As- 
sociation on  glyco-heroin,  Smith,  shows  it  to  be  a  dangerous  mixture, 
containing  the  habit-forming  drug  heroin.  It  is  exploited  in  "  patent 
medicine  style,"  and  therefore  destined  to  be  misused  by  the  unsus- 
pecting laity. — /.  Am.  M.  Assoc.,  19 14,  vol.  62,  p.  1826.. 

Hydrastinine  in  Hemorrhages  of  the  Lung.  (Roher.) — A  review 
of  the  use  of  synthetic  hydrastinine  in  case  of  pulmonary  hemorrhage. 
The  synthetic  hydrastinine  is  said  to  be  identical  with  the  natural 
substance,  and  its  toxicity  is  comparable.  The  results  in  the  five  cases 
reported  were  uniformly  satisfactory. — Therap.  Monatsh.,  1914,  vol. 
28,  pp.  505,  506. 

Idomenin. — A  combination  of  iodine,  bismuth,  and  albumin  that 
is  not  soluble  in  dilute  acid  solutions  and  is  therefore  not  decomposed 
in  the  stomach,  but  asserts  its  influence  in  the  intestinal  tract  in  the 
form  of  an  alkaline  iodide  and  bismuth  albuminate. — Therap. 
Monatsh.,  19 14,  vol.  28,  p.  512. 

Luminal. — Heinsius  suggests  that  luminal  should  have  estab- 
lished for  it  an  official  maximum  dose,  and  that  so  long  as  this  does 
not  exist  simple  cases  of  insomnia  should  be  given  from  0.05  Gm.  to 
0.1  Gm.  and  not  exceeding  0.3  Gm.  per  dose,  this  dose  to  be  repeated 
not  more  than  three  times  per  day,  with  an  interruption  of  from  one 
to  two  days  after  four  or  five  days'  treatment. — Therap.  Monatsh., 
1914,  vol.  28,  p.  514. 

Unusual  Case  of  Fatal  Poisoning  from  the  Administration  of 
Male-Fern  as  a  Vermifuge.  (Hall,  Maurice  C.) — Report  of  a  ne- 
cropsy on  a  man  who  had  died  from  an  overdose  of  the  oleoresin  of 


43Q 


Progress  in  Pharmacy. 


f  Am.  Jour.  Pharm. 
\  September,  1914. 


male-fern  administered  in  amounts  in  excess  of  the  usual  dose,  ad- 
ministration of  which  was  followed  by  castor  oil. — /.  Am.  M.  Assoc., 
1914,  vol.  63,  pp.  242,  243. 

The  Use  of  Mate.  (Editorial.) — Attention  has  recently  been 
drawn,  by  means  of  letters  to  the  Times,  to  the  use  of  leaves  known 
as  Yerba  mate,  the  tea  plant  of  South  America.  The  consensus  of 
opinion  seems  to  be  that  an  infusion  of  the  leaves  forms  a  beverage 
eminently  suited  to  a  hot,  debilitating  climate,  its  stimulating  effect 
being  no  doubt  due  to  the  caffeine  it  contains. — Pharm.  J.,  1914,  vol. 
92,  p.  870. 

Relative  Bactericidal  Power  of  Mercuric  Salts.  (Stassana  and 
Gompel.) — Mercuric  iodide  is  found  to  be  far  more  active  as  a  bac- 
tericide than  mercuric  chloride,  mercuric  cyanide,  or  mercuric  ben- 
zoate.  It  is  at  least  ten  times  more  powerful  than  mercuric  chloride, 
which  is  generally  considered  to  be  one  of  the  most  active  of  all  anti- 
septics.— Pharm.  L,  1914,  vol.  93,  p.  147. 

The  Abuse  of  Normal  Salt  Solution.  (Litchfield,  Lawrence.)  — 
The  administration  of  any  artificial  serum  as  routine  postoperative 
practice  is  questionable  therapeutics.  Too  much  water  may  fatally 
embarrass  the  heart.  Too  much  salt  may  fatally  embarrass  the  kidneys. 
When  fluids  cannot  be  taken  by  the  mouth,  thirst  may  be  relieved  by 
tap-water  or  by  isotonic  dextrose  solution  given  by  enteroclysis. — 
/.  Am.  M.  Assoc.,  1914,  vol.  63,  pp.  307-310. 

New  Technic  for  Salt  Solutions. — Faege,  K.,  outlines  a  method 
for  the  production  of  sterile  salt  solution  from  hydrant  water, 
which  depends  on  the  addition  of  hydrochloric  acid  to  ordinary 
hydrant  water  to  sterilize  it ;  then  add  sodium  hydroxide  in  the  proper 
proportion  to  produce  sodium  chloride  in  the  desired  percentage. — 
(Munch,  med.  Wchnschr.,  vol.  41,  June  106,  No.  24.)  /.  Am.  M. 
Assoc.,  1914,  vol.  63,  p.  284. 

Liquid  Petrolatum.  (Puckner,  W.  A.) — A  review  of  the  re- 
quirements for  liquid  petrolatum  made  in  the  existing  pharmaco- 
poeias, some  discussion  of  the  history  and  present  uses  of  the  prepara- 
tion, and  descriptions  of  heavy  and  light  liquid  petrolatum,  with  titles 
to  facilitate  the  dispensing  of  the  products  desired  by  the  physician. — 
/.  Am.  M.  Assoc.,  1914,  vol.  62,  pp.  1 740-1742.  (See  this  Journal, 
p.  322.) 

The  Sterilization  of  Liquid  Paraffin.  (Maughan,  D.) — From  the 
experiments  reported  it  would  appear  that  the  application  of  heat  at 
a  temperature  of  ioo°  for  half  an  hour  is  the  most  practical  method 


Am.  Jour.  Pharm.  1 
September,  1!»14.  / 


Progress  in  Pharmacy. 


431 


of  rendering  liquid  paraffin  sterile. — Pharm.  J.,  1914,  vol.  93,  pp. 
81,82. 

Paraffin  Cancer.  (Davis,  Benjamin  Franklin.) — Report  of  a 
case  of  cancer  in  one  of  the  employees  in  the  paraffin  department  of 
a  large  oil  refining  company  located  near  Chicago,  with  discussion 
of  coal  and  paraffin  products  as  causes  of  chronic  irritation  and  can- 
cer. From  a  comprehensive  review  of  the  literature  the  author  con- 
cludes that  it  would  seem  fair  to  assume  that  the  chronic-irritation 
cancer  produced  by  coal  and  petroleum  products  is  a  chemical-irrita- 
tion cancer,  and  that  it  is  not  impossible  that  the  cancer  following 
chronic  irritation  of  other  origin  may  be  of  an  essentially  similar 
nature. — /.  Am.  M.  Assoc.,  1914,  vol.  62,  pp.  1716-1720. 

Influence  of  Diet  on  the  Toxicity  of  Phosphorus.  (Opie  and 
Alford). — The  toxicity  of  phosphorus,  which  causes  fatty  degenera- 
tion of  the  liver,  is  greater  in  animals  which  have  received  a  diet  of 
meat  than  in  those  which  have  received  diets  consisting  in  large  part 
of  carbohydrates  or  of  fat. — /.  Am.  M.  Assoc.,  1914,  vol.  63,  p.  137. 

Detection  of  Picric  Acid  in  Urine.— Among  the  French  troops 
in  Algeria  a  new  form  of  malingering,  by  stimulating  the  symptoms 
of  jaundice  by  taking  picric  acid,  is  not  uncommon.  To  detect  this 
the  following  reliable  test  for  the  acid  in  the  urine  has  been  devised : 
Five  mils  of  the  urine  of  the  suspected  case  is  heated  to  boiling,  with 
an  equal  volume  of  saturated  sodium  hydroxide  solution.  Then  1 
mil  of  ammonium  sulphide  solution  is  carefully  floated  on  the  sur- 
face of  the  liquid.  In  presence  of  picric  acid,  a  red  ring  due  to  pic- 
ramic  acid  will  be  formed  at  the  zone  of  contact. —  (Repertoire,  1914, 
vol.  26,  No.  193.)    Pharm  J.,  1914,  vol.  93,  p.  195. 

Pituitary  Extract.  (Roth,  George  B.) — Report  of  an  examina- 
tion of  some  commercial  preparations  made  from  the  posterior  lobe 
of  the  pituitary  body.  The  relative  values  of  five  preparations  by 
the  blood-pressure  method  varied  from  1  to  15,  and  the  relative  value 
of  six  samples  by  the  isolated  uterus  method  from  1  to  7.5.  The  use 
of  beta-iminazolylethylamin  hydrochloride  is  suggested  as  a  standard 
for  use  on  the  isolated  uterus  method  which  is  the  only  one  appli- 
cable to  all  preparations. — /.  Am.  M.  Assoc.,  1914,  vol.  63,  pp.  476- 
479-  » 

Prophylactic  Use  of  Quinine  in  Malaria.  (Carter,  H.  R.) — The 
use  of  quinine  in  small  doses  is  an  efficient  method  for  preventing 
malarial  fever.  This  method  is  especially  adapted  for  use  in  a  farm- 
ing community  where  it  is  not  practicable  economically  to  get  rid  of 


432 


Progress  in  Pharmacy. 


(km.  Jour.  Pharm. 
\  September,  1914. 


malarial  mosquitoes  or  to  properly  screen  against  them. — /.  Am. 
M.  Assoc.,  1914,  vol.  62,  p.  2042. 

Quinine  in  the  Treatment  of  Syphilis.  (Breitmenn,  M.  J.) — The 
observation  that  the  administration  of  quinine  for  the  treatment  of 
malaria  in  patients  infected  with  syphilis  was  invariably  accompanied 
by  marked  improvement  of  secondary  and  tertiary  manifestations  of 
the  latter  disease  led  to  further  experimentation  and  the  use  of  a 
mixture  of  quinine  muriate  3,  with  antipyrin  2,  dissolved  in  from  6 
to  8  c.c.  of  warm  water.  This  mixture,  designated  chinopyrin,  is  in- 
jected subcutaneously  and  has  given  promising  results. — Therap. 
Monatsh.,  1914,  vol.  28,  pp.  504,  505. 

Results  of  Radium  in  Cancer.  (Janeway,  H.  H.) — A  survey  of 
reported  results,  with  the  suggestion  that  a  more  successful  method 
of  applying  radium  may  yet  be  discovered  and  that  the  whole  question 
may  reduce  itself  to  the  even  distribution  of  the  proper  dosage 
throughout  all  invol-ved  tissues.  At  the  present  time  radium  may 
only  supplement  but  not  replace  the  knife. — /.  Am.  M.  Assoc.,  1914, 
vol.  62,  pp.  1 707-1 709. 

Dangers  from  Radium  Treatment  of  Cancer.  (Rovsing,  T.)  — 
Tragic  experiences  in  a  number  of  cases  lead  to  the  conclusion  that 
radium  promotes  instead  of  checks  cancer. — Hospitalstid.,  1914, 
vol.  62,  >N.  27.)    /.  Am.  M.  Assoc.,  1914,  vol.  63,  p.  520. 

Production  of  Metallic  Uranium.  {Anon.) — The  steady  increase 
in  the  production  of  radium  at  S.  Joachimsthal,  Austria,  has  resulted 
in  an  overproduction  of  uranium  salts,  which  up  to  the  present  time 
are  used  only  as  coloring  for  glass  and  porcelain  and.  have,  therefore, 
but  a  limited  application.  Attempts  have  recently  been  made  to  pro- 
duce metallic  uranium  by  an  electrolytic  method,  and  these  efforts 
promise  to  be  successful.  Further  experiments  are  being  undertaken 
with  a  view  to  utilizing  the  resulting  material  in  the  production  of 
amalgams,  more  particularly  the  utilization  of  metallic  uranium  in 
the  improvement  of  steel. — Pharm.  Post,  1914,  vol.  47,  p.  557. 

Pharmacological  Instability  of  Scopolamine  in  Ampoules. 
(Langer,  H.) — To  determine  the  pharmacological  activity  of  scopo- 
lamine solutions,  recourse  was  had  to  its  antidotal  action  on  muscarine 
in  the  isolated  frog's  heart.  This  test  is  quantitative,  and  much  more 
reliable  than  the  production  of  mydriasis  in  the  cat's  eye.  From  tests 
with  the  muscarine  method,  it  is  found  that  scopolamine  salts  kept 
in  ampoules  soon  deteriorate,  losing  their  specific  action.  Solutions 
of  scopolamine  for  therapeutic  use,  therefore,  should  be  freshly  pre- 


Am.  Jour.  Pharm.  ) 
September,  1914.  j 


Progress  in  Pharmacy. 


433 


pared,  and  the  employment  of  those  in  sterilized  ampoules  avoided  as 
far  as  possible. — Pharm.  J.,  1914,  vol.  93,  p.  147. 

Recordin. — Mannich  and  Leemhuis,  from  the  pharmaceutical 
laboratory  of  the  University  of  Gottingen,  report  the  examination  of 
a  preparation  marketed  as  a  prophylactic  for  the  ills  of  old  age,  in- 
cluding arteriosclerosis.  The  analysis  showed  the  substance  to  consist 
largely  of  sodium  chloride,  with  negligible  quantities  of  phosphates, 
sulphates,  carbonates,  and  tartrates  of  calcium,  magnesium,  and 
sodium.  As  diluents  bolus  and  starch  were  used. — Apoth.-Ztg.,  1914, 
vol.  29,  p.  628. 

Rhubarb.  (Rosenthaler,  L.) — A  review  of  some  of  the  available 
literature  relating  to  the  drying  of  rhubarb,  from  which  the  author 
concludes  that  this  drug  is  always  dried  spontaneously,  either  out  of 
doors  or  suspended  in  houses.  The  absence  of  gelatinized  starch 
in  the  root  indicates  that  higher  temperatures  are  never  used. — 
Schzveiz.  Apoth.-Ztg.,  1914,  vol.  52,  pp.  405,  406. 

The  Control  of  Saccharin  and  Analogous  Substances. — The  sov- 
ereigns and  heads  of  the  Governments  of  Germany,  Belgium,  Greece, 
France,  Italy,  the  Netherlands,  Portugal,  and  Russia,  desiring  to  regu- 
late the  use  of  saccharin  and  allied  substances,  have  agreed  on  articles 
describing  the  substances  referred  to,  and  have  undertaken  to  prohibit 
the  use  of  saccharin  and  other  allied  products  in  all  beverages  and 
foodstuffs. — Perf.  and  Ess.  Oil  Rec,  1914,  vol.  5,  pp.  288,  289. 

Scillitin,  the  Toxic  Principle  of  Squill. — Kopaczewski,  W.,  says 
he  has  isolated  the  toxic  principle  of  squill  in  the  form  of  an  amor- 
phous glucoside,  C17H25Oe,  to  which  the  name  scillitin  is  given.  It 
is  a  very  light,  non-hygroscopic,  intensely  bitter  powder.  It  is  soluble 
in  the  saturated  alcohols  of  the  fatty  series ;  sparingly  soluble  in 
water,  and  insoluble  in  ordinary  organic  liquids.  It  melts  at  1 52°  to 
1 540. — Pharm.  J.,  19 14,  vol.  92,  p.  879. 

Sennatin.  (Lindbom,  Oskar.) — The  intramuscular  injection  of 
sennatin  produces,  in  the  majority  of  cases  of  constipation,  copious 
stools,  with  subjective  and  sensible  peristaltic  movements  of  the  intes- 
tine. As  an  occasional  complication  marked  increase  in  temperature 
was  noted. — Therap.  Monatsh.,  1914,  vol.  28,  p.  509. 

The  Tablet  Industry,  its  Evolution  and  Present  Status,  the  Com- 
position of  Tablets  and  Methods  of  Analysis.  (Kebler,  L.  F.) — 
Historical  review,  with  a  report  on  the  examination  of  a  number  of 
samples  showing  considerable  variation  in  the  nature  of  the  tablets 
examined. — /.  Am.  Pharm.  Assoc.,  1914,  vol.  3,  pp.  820-848,  937- 
958,  1 062-1 099. 


434 


Progress  in  Pharmacy. 


{Am.  Jour,  Pharm, 
Septeiiober,'1914. 


Compressed  Tablets.  (Rohn,  R.)- — For  the  production  of  com- 
pressed tablets  that  will  readily  disintegrate,  the  addition  of  from  10 
to  20  per  cent,  of  magnesium  peroxide  is  suggested.  Tablets  with 
this  addition,  when  moistened  with  water,  will  disintegrate  almost 
immediately. — Sudd.  Apo'th.-Ztg.J  1914,  vol.  54,  p.  398. 

Urease.  (Puckner,  W.  A.) — Urease  is  a  preparation  of  the  urea- 
lytic  enzyme  obtained  from  the  soy  bean,  Soja  hispida.  It  decom- 
poses urea  into  ammonia  and  carbon  dioxide,  and  it  may  be  employed 
in  the  determination  of  the  amount  of  urea  in  the  urine,  blood,  and 
other  body  fluids.  Urease  is  now  being  marketed  by  several  firms  as 
a  fine,  white  powder  with  little  taste  or  odor.  It  is  soluble  in  slightly 
alkaline  water,  and  represents  the  urea-converting  enzyme  of  soy 
bean  in  a  condition  of  high  potency.  It  is  practically  free  of  the 
water-soluble  proteins  which  are  precipitated  by  hydrochloric  acid, 
and  of  proteins  that  are  insoluble  in  water. — /.  Am.  M.  Assoc.,  1914, 
vol.  63,  p.  165. 

Urotropin, — Simon  reports  six  cases  in  which  hematuria  fol- 
lowed the  administration  of  fairly  large  doses  of  urotropin.  In  rab- 
bits hematuria  could  be  produced  only  by  the  administration  of  very 
large  doses :  8  Gm.  per  day. — Therap.  Monatsh.,  1914,  vol.  28,  p.  544. 

Uteraniin, — Uteramin  is  a  new  name  applied  to  paraoxy- 
phenylethylamine,  formerly  sold  under  the  name  systogen. — Therap. 
Monatsh.,  1914,  vol.  28,  p.  511. 

IVassermann  Reaction  in  Tuberculosis.  (Letulle  and  others.)  — 
It  was  found  that  19  per  cent,  of  346  tuberculosis  inmates  of  the 
Boucicaut  Hospital  gave  a  positive  response  to  the  Wassermann  test. 
Only  ten  of  the  total  of  64  reacting  were  aware  of  their  syphilitic 
taint  or  had  signs  of  it.  Fourteen  of  the  patients,  including  eight 
under  36,  had  some  aorta  affection. — Bull.  Acad.  Med.,  1914,  vol. 
8,  No.  4.)   /.  Am.  M.  Assoc.,  19 14,  vol.  62,  p.  1848. 


NEWS  ITEM. 

The  National  Association  of  Retail  Druggists  ended  in 
Philadelphia  on  August  21  the  largest  convention  of  druggists  ever 
held  in  this  country.  Fully  1 500  delegates,  representing  20,000  mem- 
bers of  the  association,  were  present.  The  following  officers  were 
elected :  President,  Samuel  C.  Henry ;  Vice  Presidents,  A.  S.  Ludwig, 
W.  H.  Humphreys  and  T.  C.  Coltman ;  Secretary,  Thomas  H.  Potts ; 
Treasurer,  Grant  W.  Stevens ;  Executive  Committee,  James  F.  Fin- 
nerman,  Robert  J.  Frick  and  T.  S.  Armstrong. 


THE  AMEKIOAN 


OF  PHARMACY 


THE  EXAMWATION  OF  SOME  DRUGS  WITH  SPECIAL 
REFERENd^S^^E/NHYDROUS  ALCOHOL  AND 
ETWrt^TRACTS  AND  ASH.* 

By  J.  R.  Rippetoe,  Analysts  N.  Smith,  W.  Taylor,  and  G.  Stoddart. 

As  announced  in  the  first  paper  bearing  the  above  title,1  in  the 
examination  of  a  number  of  commercial  samples  of  vegetable  drugs, 
in  addition  to  identifying  the  samples  and  making  specified  tests  for 
added  or  accidental  impurities,  such  as  starch,  etc.,  we  have  attempted 
to  make  some  assays  that  would  serve  as  a  means  for  determining 
the  relative  value  of  the  sample  when  compared  with  some  other 
sample  or  standard. 

These  assays  have  consisted  chiefly  in  determining  anhydrous 
extracts,  alcohol  and  water,  ether,  chloroform,  or  petroleum  ether, 
as  may  be  suggested  by  the  nature  of  the  drug. 

Since  the  appearance  of  the  first  paper  we  have  examined  a 
number  of  drugs  along  the  same  lines.  The  results  of  this  work  are 
given  in  the  list  appended,  which  list  not  only  includes  many  of  the 
names  appearing  in  the  first  paper  but  also  many  drugs  not  heretofore 
considered. 

For  some  drugs  the  value  of  determining  the  amount  of  an- 
hydrous matter  that  may  be  extracted  with  various  solvents  has  been 
pretty  well  established,  also  the  determination  of  ash.  This  has  been 
recognized  by  the  Ninth  Revision  Committee  of  the  U.  S.  P.,  and  it 
is  indicated  2  that  a  large  number  of  official  drugs  are  to  have  an- 
hydrous or  volatile  extract  and  ash  standards. 

*  Second  Paper. 

1  First  paper,  Rippetoe  and  R.  Minor,  this  Journal,  October,  1912,  pp.  433- 

445- 

2  /.  A.  Ph.  A.,  March,  1914,  p.  359. 

(435) 


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444  The  Detection  of  Emo  din-Bearing  Drugs.  \Am^J-J^m- 

The  methods  for  assaying  the  drugs  reported  in  this  paper  are 
essentially  the  same  as  previously  given. 

For  further  particulars  the  reader  is  referred  to  the  first  paper 
appearing  in  the  October,  191 2,  number  of  this  Journal. 

The  results  of  the  assays  are  given  in  the  table  on  pp.  436-443. 

Abbreviations,  etc. :  Wi. — Whole  drug ;  P. — Powdered  drug ;  G. — 
Ground  drug.  Where  the  alcoholic  menstruum  used  in  determining 
the  anhydrous  alcohol  extract  was  of  a  percentage  other  than  95  oer 
cent,  absolute  alcohol,  the  percentage  is  indicated  by  the  figure  in 
brackets;  for  example,  20.3  (49),  32.6  (63)  indicating  49  and  63  per 
cent,  absolute  alcohol,  respectively. 

Agar- Agar — Four  samples  contained  ash  8.23,  4.8,  4.5  and  4.4 
per  cent,  respectively. 

Gambir — Fifteen  samples  :  Alcohol  Extract — Minimum  63.30  per 
cent.,  maximum  87.00  per  cent.,  average  78.6  per  cent.  Aqueous 
Extract — Minimum  61.7  per  cent.,  maximum  82.75  per  cent.,  average 
77.95  per  cent.  Ash — Minimum  3.40  per  cent.,  maximum  8.48  per 
cent.,  average  5.55  per  cent. 

Ipecac — Eight  samples:  Ash  minimum  3.40  per  cent.,  maximum 
4.63  per  cent.,  average  4.10  per  cent. 

Jalap — Seven  samples  :  Ash  minimum  0.62  per  cent.,  maximum 
1.77  per  cent.,  average  1.29  per  cent. 

Lyco  podium — One  sample  contained  8.61  per  cent,  ash,  which  was 
chiefly  calcium  carbonate. 

Salep — One  sample  ash  2.24  per  cent. 

Taraxacum — One  sample  submitted  consisted  of  approximately 
50  per  cent,  chicory. 

Analytical  Department, 
Schieffelin  &  Co.,  New  York. 


THE  DETECTION  OF  EMODIN-BEARING  DRUGS  IN  PRES- 
ENCE OF  PHENOLPHTHALEIN. 

By  L.  E.  Warren. 

Phenolphthalein,  either  alone  or  in  mixture  with  other  drugs,  is 
a  constituent  of  a  number  of  nostrums  which  are  sold  as  laxatives. 
The  separation  and  identification  of  phenolphthalein  in  medicines  is 
usually  accomplished  readily,  but  its  presence  may  interfere  with  the 


%'ctob£"  imm'}        Detection  of  Emo  din-Bearing  Drugs.  445 


identification  of  other  drugs.  This  is  likely  to  be  the  case  with  cascara, 
senna,  and  other  emodin-bearing  drugs.  Ordinarily  the  emodin- 
bearing  drugs  as  a  class  would  be  detected  by  shaking  the  faintly 
acidified  extracts  with  benzol  and  washing  the  solvent  first  with  water, 
which  is  discarded,  and  then  with  very  dilute  ammonia  water.1  In 
presence  of  emodin  the  ammoniacal  layer  becomes  red,  the  depth  of 
color  and  shade  depending  somewhat  upon  the  amount  of  emodin 
present  and  the  source  of  the  drug  from  which  obtained.  This  test 
cannot  be  used  in  presence  of  phenolphthalein  because  this  substance 
behaves  like  emodin.  This  holds  true  in  spite  of  the  great  insolubility 
of  phenolphthalein  in  water,2  for  if  a  solution  containing  this  sub- 
stance be  acidified,  diluted  with  several  times  its  volume  of  water  and 
filtered,  the  filtrate  will  become  strongly  colored  purplish-red  on  the 
addition  of  ammonia  water  or  of  potassium  hydroxide  or  sodium 
hydroxide  solution.  Or  if  the  acid  filtrate  be  shaken  with  benzol,  the 
aqueous  layer  discarded,  and  the  solvent  washed  with  either  of  these 
alkaline  solutions,  the  purplish-red  color  appears  at  once.  Unless  the 
quantity  of  phenolphthalein  be  very  small  the  color  produced  by  it 
with  the  alkalies  will  hide  or  obscure  that  of  any  emodin  alkali  com- 
pounds that  may  be  present. 

Under  certain  conditions,  however,  the  color  produced  by  phenol- 
phthalein and  an  excess  of  the  fixed  alkali  hydroxides  gradually  dis- 
appears, owing  to  the  formation  of  the  trimetallic  salt  of  phenol- 


^orntrager:  Z.  anal  Chem.,  ig,  165  (1880). 

2  According  to  McCoy  (Am.  Chem.  Jour.,  31,  503,  1904),  the  maximum 
solubility  of  phenolphthalein  in  water  is  approximately  a  ten-thousandth- 
normal  solution.  This  is  equivalent  to  about  0.0032  Gm.  of  the  substance  in 
100  c.c.  This  conclusion  was  reached  after  approximate  determinations  had 
been  carried  out  by  two  methods.  In  one  0.0318  Gm.  of  purified  phenol- 
phthalein was  boiled  with  1200  c.c.  of  water.  On  cooling  no  deposit  formed, 
indicating  a  solubility  greater  than  twelve-thousandth-normal.  In  the  other 
known  amounts  of  tenth-normal  phenolphthalein  (in  alcohol)  were  added  to 
100  c.c.  of  five-hundredth-normal  ammonia  water  and  the  solution  neutralized 
by  the  addition  of  2  c.c.  of  tenth-normal  hydrochloric  acid.  With  0.5  c.c.  of 
the  phenolphthalein  solution  the  resultant  solution  contained  a  precipitate  of 
phenolphthalein ;  with  0.3  c.c.  the  solution  was  turbid ;  with  0.2  c.c.  faintly 
turbid ;  and  with  0.1  c.c.  clear,  although  a  slight  deposit  ^formed  on  standing 
over  night.  This  indicated  a  solubility  of  about  ten-thousandth-normal,  cor- 
responding to  0.00318  Gm.  per  100  c.c.  On  the  other, hand,  Zotier  (Bull.  soc. 
chim.  [4],  7,  993,  1910),  from  an  average  of  thirty  determinations  (method 
not  stated),  gives  the  solubility  of  phenolphthalein  in  water  as  about  0.0092 
Gm.  in  100  c.c. 


446  The  Detection  of  Emo  din-Bearing  Drugs.  {A™'cto™r  Su™' 

phthalein,  leaving  the  solution  colorless.  On  the  other  hand,  the  color 
of  the  alkali  compounds  with  emodin  is  more  stable,  sometimes  last- 
ing for  several  days.*  An  attempt  was  made  to  differentiate  by  this 
test  between  phenolphthalein  and  emodin  when  in  mixture,  but 
the  results  were  not  very  satisfactory.  If  applied  to  a  mixture  of 
phenolphthalein  and  an  extract  of  an  emodin-bearing  drug,  obtained 
by  extraction  with  alcohol  and  evaporation  of  the  solvent,  the  ex- 
tracted coloring  matter  renders  the  test  worthless.  If  applied  to  a 
benzol,  chloroform,  or  ether  extract,  the  confusion  of  colors  renders 
positive  identification  doubtful.  However,  if  the  red  color  of  the 
strongly  alkaline  solution  disappears  the  test  is  a  valuable  confirma- 
tion of  the  absence  of  most  of  the  emodin-bearing  drugs.  If  the 
color  persists  after  standing  for  several  hours,  the  presence  of  an 
emodin-bearing  drug  is  presumptive.  A  method  seemed  desirable 
by  which  the  phenolphthalein  might  be  removed  from  such  mixtures, 
thus  leaving  the  emodin  free  to  be  tested  for  in  the  usual  way.  Of  the 
several  methods  used  for  its  quantitative  determination,  that  proposed 
by  Kollo,3  by  which  the  substance  is  precipitated  as  tetraiodophenol- 
phthalein,4  seemed  the  most  promising. 

Some  tests  were  first  made  with  a  preparation  known  to  contain 
phenolphthalein  (most  of  which  was  in  suspension)  and  an  emodin- 
bearing  drug  extract. 

The  following  method  was  used : 

The  preparation,  which  was  in  the  form  of  a  syrup,  was  diluted 
with  water,  faintly  acidified  and  filtered  to  remove  most  of  the  phenol- 
phthalein. The  filtrate  was  neutralized  with  ammonia  water,  evap- 
orated to  a  very  thick  syrup,  and  the  warm  syrup  extracted  with 
acetone  (which  had  been  rendered  slightly  acid  by  hydrochloric  acid) 
by  stirring  with  successive  small  portions  of  the  solvent  and  decanting 
from  the  residue.  In  this  case  acetone  was  found  a  more  suitable 
solvent  than  either  chloroform  or  ether,  as  it  formed  less  troublesome 
emulsions.  In  preparations  that  do  not  form  emulsions  ether  extracts 
are  more  satisfactory  for  the  subsequent  manipulations.  The  acetone 
fractions  were  united,  evaporated  to  dryness  on  the  water-bath,  the 

*  Experiments  have  shown  that  if  ether  extracts  from  small  amounts 
of  rhubarb  be  heated  on  the  water-bath  for  three  hours  with  50  per  cent, 
sodium  hydroxide  solution  the  red  color  is  not  destroyed. 

sAp.  Ztg.,  24,  283  (1909). 

4  Tetraiodophenolphthalein  was  first  described  by  Classen  and  Loeb  (Ber., 
28,  1603,  1895). 


Am6ctobUerr,  \9um' }  The  Detection  of  Emo  din-Bearing  Drugs.  447 

residue  twice  moistened  with  alcohol  and  evaporated  in  order  to  re- 
move the  last  trace  of  acetone.  The  residue  was  taken  up  in  diluted 
sodium  hydroxide  solution,  the  solution  filtered,  and  a  slight  excess 
of  iodine  test  solution  added,  followed,  after  a  few  minutes,  by  a 
slight  excess  of  hydrochloric  acid.  The  container  was  cooled  for  an 
hour  in  a  water-bath  having  a  temperature  below  150  C.  and  the  con- 
tents filtered.  By  this  treatment  the  phenolphthalein  was  precipitated 
as  tetraiodophenolphthalein,  a  substance  which  is  very  insoluble  in 
water.  The  precipitate  on  the  filter  was  washed  with  water  several 
times,  a  yellow  solution  being  produced.  The  filtrate  and  washings 
were  united,  the  solution  treated  with  a  slight  excess  of  sodium  sul- 
phite to  remove  free  iodine,  and  the  solution  shaken  with  chloroform. 
The  chloroform  was  evaporated  and  the  residue  treated  with  dilute 
solution  of  sodium  hydroxide.  By  this  treatment  the  anthracene  pur- 
gatives give  red  colors  which  vary  in  shade,  depending  somewhat  upon 
the  source  of  the  emodin.  Preparations  containing  phenolphthalein 
alone  give  no  red  color,  or  at  most  a  faint  purplish-red,  which  soon 
fades  if  a  considerable  excess  of  the  alkali  be  added. 

Briefly  stated,  the  method  consists  in  treating  an  acetone  or  ether 
extract  of  the  substance  with  sodium  hydroxide  solution,  adding 
iodine  solution,  followed  by  hydrochloric  acid,  removing  the  tetraiodo- 
phenolphthalein by  filtration  after  standing,  shaking  out  the  filtrate 
with  chloroform  after  adding  a  sulphite  to  remove  excess  of  iodine, 
evaporating  the  chloroform,  and  treating  the  residue  with  sodium 
hydroxide  solution. 

As  controls  the  test  was  carried  out  with  the  fluidextracts  of 
cascara  and  rhubarb,  a  mixture  of  the  fluidextracts  of  senna  and 
licorice,  a  trade  preparation  stated  to  contain  senna,  a  mixture  con- 
taining aloes  and  phenolphthalein,  and  a  trade  preparation  claimed  to 
be  a  form  of  bitterless  cascara.  The  residue  from  the  fluidextract 
of  cascara  gave  a  dark  red  color  with  a  faint  brownish  tinge,  that 
from  rhubarb  a  deep  red  with  a  suggestion  of  purplish,  that  from 
the  senna-licorice  mixture  a  somewhat  lighter  red  with  a  faint  sug- 
gestion of  yellowish  (the  licorice  did  not  interfere),  that  from  senna 
alone  a  color  similar  to  that  from  the  mixed  senna  and  licorice,  that 
from  the  aloes  and  phenolphthalein  a  faint  reddish-yellow,  and  that 
from  the  bitterless  cascara  preparation  a  color  similar  to  that-  given 
by  the  fluidextract  of  cascara.  The  test  with  aloes  was  carried  out 
several  times,  but  with  results  that  were  not  entirely  satisfactory.  The 
colors  given  for  the  several  drug  residues  do  not  differ  from  each 


448  The  Detection  of  Em 0 din-Bearing  Drugs.  {\tJ0°buer;  f9urm' 

other  sufficiently  to  positively  identify  the  source  of  the  drug,  yet 
they  should  prove  of  considerale  value  as  confirmatory  evidence.  The 
light  red  from  senna  would  not  ordinarily  be  mistaken  for  the  deeper 
red  of  cascara  or  of  rhubarb,  nor  the  faint  reddish-yellow  of  aloes  for 
any  of  the  others,  particularly  if  controls  be  carried  out.  In  some 
instances,  on  standing,  a  reddish,  flocculent  precipitate  was  formed 
in  the  alkaline  solutions  as  finally  obtained.  On  its  removal  by  filtra- 
tion the  filtrate  became  lighter  in  color.  In  the  test  with  the  aloes- 
phenolphthalein  mixtures  the  filtrate  became  of  a  reddish-yellow 
color.  On  the  whole  the  test  is  much  less  satisfactory  for  aloes  than 
for  the  other  drugs  tested. 

While  these  experiments  were  in  progress  Bailey  5  published  a 
method  of  distinguishing  chrysophanic  acid  of  rhubarb  from 
phenolphthalein.  By  his  method  the  dealcoholized,  faintly  acidified 
preparation  is  shaken  with  ether,  and  the  solvent  layer  washed  with 
very  dilute  ammonia  water.  The  alkaline  solution  is  allowed-  to 
stand  over  night,  by  which  the  colored  compounds  of  haematoxylon 
and  curcuma,  if  present,  fade.  The  solution  is  then  acidified  and 
shaken  with  ether.  Only  chrysophanic  acid  and  phenolphthalein  pass 
into  the  solvent.  The  ether  is  evaporated  and  the  residue  boiled  with 
zinc  dust  and  potassium  hydroxide  solution  until  the  red  color  has 
entirely  disappeared.  By  this  treatment  chrysophanic  acid  is  reduced, 
*he  solution  becoming  yellowish,  and  phenolphthalein  is  reduced  to 
phenolphthalin.  The  solution  is  diluted  with  water,  or  a  drop  of 
hydrogen  peroxide  solution  is  added.  A  cherry-red  color  appearing 
at  once  indicates  chrysophanic  acid.  Under  these  conditions  phenol- 
phthalin is  not  oxidized. 

Bailey  did  not  apply  his  method  to  cascara  or  to  aloes,  but  implies 
that  it  might  be  used  on  senna  preparations.  We  have  applied  the 
method  to  the  fluidextracts  of  senna  and  cascara,  to  each  of  which 
some  alcoholic  solution  of  phenolphthalein  had  been  added.  In  each 
case  the  result  was  satisfactory.  It  was  found  necessary  to  boil  the 
alkaline  zinc-dust  mixture  for  some  time  in  order  to  completely 
destroy  the  red  color.  It  was  also  found  that  exposure  of  the  boiled 
solution  to  the  air,  as  in  filtration,  was  generally  sufficient  to  restore 
the  color  to  the  substance.  When  the  test  was  applied  to  Barbadoes 
aloes  1?he  red  color  given  on  the  addition  of  hydrogen  peroxide  solu- 
tion was  slow  to  appear  and  was  masked  considerably  by  yellow  color- 
ing matters.    To  the  limited  extent  that  comparison  tests  have  been 


5  Jour.  Ind.  Eng.  Chem.,  6,  320  (1914). 


Am.  Jour.  Pharm.  ) 

October,  1914.  J 


Red  Gum. 


449 


carried  out  it  does  not  appear  that  either  method  has  any  marked 
advantage  over  the  other.  If  haematoxylon  or  curcuma  be  present, 
results  may  be  obtained  more  quickly  by  the  proposed  iodine  method, 
since  the  colors  from  these  substances  are  destroyed  (or  removed)  by 
the  iodine  treatment,  hence  it  is  unnecessary  to  wait  over  night  for  the 
destruction  of  the  coloring  matters  by  treatment  with  ammonia. 

Summary. — The  presence  of  phenolphthalein  in  medicines  inter- 
feres with  the  detection  of  the  emodin-bearing  drugs. 

Phenolphthalein  may  be  removed  by  treating  the  ether  (or 
acetone)  extract  with  sodium  hydroxide  and  iodine  solutions,  adding 
hydrochloric  acid  and  filtering. 

After  removal  of  the  phenolphthalein  the  emodin  may  be  de- 
tected in  the  usual  way,  using  a  fixed  alkali  hydroxide  for  its  solution. 

The  method  was  tried  on  several  emodin-bearing  drugs  and  gave 
satisfaction,  except  in  the  case  of  aloes. 

Laboratory  of  the  American  Medical  Association. 


RED  GUM. 

By  John  K.  Thum,  Pharmacist  at  German  Hospital,  Philadelphia. 

Eucalyptus  rostrata  yields  the  extract  Australian  Kino,  and  more 
popularly  known  by  the  name  "  Red  Gum."  The  latter  is  found 
on  the  market,  pharmaceutically,  in  the  form  of  troches  and  in  a 
fluid  form,  misleadingly  termed  by  the  manufacturers  a  fluidextract. 

Like  Kino  of  the  U.  S.  P.,  it  contains  considerable  tannin,  which 
makes  it  extremely  valuable  as  an  astringent.  The  so-called  fluid- 
extract  has  obtained  some  vogue  among  throat  specialists  as  a  local 
application  in  place  of  the  well-known  Glyceritum  Tannin,  it  being 
much  more  agreeable  and  pleasant  to  the  patient,  and  just  as  efficient 
as  the  latter  preparation. 

While  all  the  manufacturers  who  market  a  fluid  form  of  red  gum 
have  it  listed  in  their  price  lists  as  a  fluidextract,  some  have  an 
asterisk  placed  alongside  the  word,  -and  on  referring  to  the  footnote 
one  finds  these  words :  "  those  fluids  which  do  not  represent  the 
crude  drug,  minim  for  grain  ";  which  is  a  tacit  confession  that  it  is 
impossible  to  make  a  100  per  cent,  solution  of  this  drug. 

On  looking  over  the  literature  relating  to  this  drug — and  the 
literature,  by  the  way,  is  scant — one  is  informed  that  it  is  soluble 
in  cold  water  to  the  extent  of  80  to  90  per  cent.   This  is  wrong.   It  is 


450  -  Analyses  of  Two  Echinacea  Roots.  SJ™' 

extremely  doubtful  if  as  much  as  30  per  cent,  is  soluble  in  cold  or 
even  boiling  water.  My  experience  leads  me  to  believe  that  less  than 
20  per  cent,  of  the  drug  is  soluble  in  boiling  water,  and  that  it  refuses 
to  remain  in  solution  without  the  addition  of  varying  amounts  of 
glycerin;  without  this  addition  gelatinization  always  results.  My 
experience  also  showed  that  the  use  of  alcohol  in  effecting  solution 
is  unnecessary,  or  at  least  less  effective  than  a  menstruum  consisting 
of  water  and  glycerin.  Heat  must  be  used.  I  found  that  after 
shaking  20  parts  of  the  powdered  drug  with  80  parts  of  cold  water, 
at  intervals,  for  twelve  hours,  two  parts  of  drug  remained  in  solution. 
By  heating  in  a  flask  on  a  water-bath  for  15  minutes  and  frequently 
shaking,  about  10  per  cent,  is  dissolved.  Unfortunately,  after  a  few 
days  a  jelly-like  mass  results.  This,  however,  as  mentioned  above, 
can  readily  be  overcome,  or  rather  avoided,  by  the  addition  of  glycerin 
or,  better  still,  by  heating  on  a  water-bath  with  equal  parts  of 
glycerin  and  water. 

After  more  or  less  experimentation,  which  I  need  not  recount 
here,  I  evolved  the  following  formula  and  method  of  procedure, 
which  seems  to  meet  all  the  requirements  of  those  physicians  who 
wish  to  use  red  gum  as  a  local  application : 

Red  Gum,  powdered   200  Gm. 

Glycerin   .   250  Cc. 

Water,  a  sufficient  quantity  to  make.  .  1000  Cc. 

Mix  the  glycerin  with  five  hundred  cubic  centimetres  of  water, 
and  triturate  the  powdered  red  gum  with  sufficient  of  the  mixture 
to  produce  a  smooth  paste.  Transfer  this  to  a  flask  by  the  aid  of 
the  remainder  of  the  mixture  of  glycerin  and  water  and  heat  on  a 
water-bath  for  one  hour ;  filter  through  purified  cotton,  keeping  the 
funnel  well  covered.  Finally,-  pass  sufficient  water  through  the 
filter  to  obtain  one  thousand  cubic  centimetres  of  fluid. 


ANALYSES  OF  TWO  ECHINACEA  ROOTS. 
By  F.  W.  Heyl  and  J.  F.  Staley. 

A  review  of  the  literature  indicates  that  a  further  chemical  study 
of  Echinacea,  particularly  of  Brauneria  angustifolia,  might  be  of 
some  value  in  offering  evidence  concerning  the  conflicting  views  con- 
cerning the  pharmaceutical  value  of  this  plant. 


October  i9i4rm' j     Analyses  of  Two  Echinacea  Roots.  451 

This  root  has  been  stated  1  to  contain  minute  quantities  of  an 
inactive  alkaloid.  Its  supposed  medicinal  activity  is  ascribed  to  the 
presence  of  a  resin.  Lastly,  in  describing  the  pharmacognosy  of 
Echinacea,2  Henry  Kraemer  and  Maud  Sollenberger  have  found 
inulin, 

Despite  the  unfavorable  report  of  the  American  Medical  Associa- 
tion, Council  on  Pharmacy  and  Chemistry,3  this  plant  is  used  to  some 
extent,  and  a  review  of  the  meagre  chemical  literature  indicates  that 
more  experimental  evidence  is  required  before  forming  a  conclusion 
concerning  its  value  pharmaceutically. 

In  this  brief  paper  we  report  the  results  of  the  proximate  analyses 
of  two  species,  and  further  work  is  in  progress  upon  the  more  im- 
portant Brauneria  angustifolia.  The  sample  of  Brauneria  purpurea 
was  obtained  upon  the  market  as  a  sample  of  Echinacea. 

Experimental. 

The  material  for  this  investigation  consisted  of  the  roots  of  two 
species  of  the  genus  Brauneria  {Echinacea)  of  the  family  Com- 
posite, (a)  Brauneria  angustifolia  (D.  C.)  Heller,  the  narrow-leaved 
purple  cone  flower,  and  (b)  Brauneria  purpurea  (D.  C.)  Britton, 
the  purple  cone  flower. 

The  Echinacea  of  the  U  S.  Dispensatory,4  in  so  far  as  it  applies 
to  "  Brauneria  pallida  (Nutt.)  Britton/'  is  a  confusion  of  two  species. 
The  "  Echinacea  angustifolia  D.  C."  there  considered  a  synonym  of 
the  above  (B.  pallida)  is  now  known  to  be  a  separate  and  distinct 
species,  Brauneria  angustifolia  (D.  C.)  Heller,  and  has  from  our  ob- 
servations furnished  most  of  the  Echinacea  of  the  market.  It  is  this 
species  which  furnishes  the  principal  material  under  investigation. 
The  recognition  of  this  confusion  leaves  Brauneria  pallida  (Nutt.) 
Britton  as  a  species  of  good  standing.5 

The  roots  of  Brauneria  angustifolia  were  collected  for  us  in  the 
rough  gravelly  prairie  land  of  north  central  Kansas.  The  Brauneria 
purpurea  was  said  to  have  been  collected  in  Missouri. 

The  roots  of  Brauneria  angustifolia  were  received  at  the  labora- 

1C.  G.  Lloyd,  Eclec  Med.  Journal  (1897). 

2  American  Journal  Pharmacy,  83,  315  (1911). 

3  Journal  A.  M.  A.,  vol.  53,  1836  (1909). 

4  U.  S.  Dispensatory,  p.  1476  (19th  Ed.). 

5  Robinson,  B.  L.,  and  Fernald,  M.  L. :  "  Gray's  New  Manual  of  Botany," 
1908,  p.  832/ 

Britton,  N.  L.,  and  Brown,  A. :  "  Illustrated  Flora,"  1913,  p.  476. 


452  Analyses  of  Two  Echinacea  Roots.     {AmoJobIr  Su™' 

tory  in  the  green  condition,  and  after  careful  identification  by  Dr. 
L.  H.  Harvey,  to  whom  we  are  indebted  for  the  botanical  work,  were 
ground  while  still  fresh.  A  large  quantity  of  this  material  was  trans- 
ferred to  percolators  and  exhausted  with  95  per  cent,  alcohol,  as  will 
be  described  later. 

A  small  sample  was  air-dried,  and  then  ground  and  sieved.  This 
was  used  for  the  proximate  analyses.  The  Brauneria  purpurea  was 
received  in  the  air-dried  condition  and  ground  and  sieved  by  us. 

The  roots  were  quantitatively  extracted,  with  the  following 
results : 

Extract.  B.  angustifolia.         B.  purpurea. 

Ligroin  (35°-55°J    077  0.93 

Ether  (no°)    1.26-  1.18  1.61 

Alcohol    (iio°)   1970-19.94  18.28 

The  proximate  analyses  were  conducted  in  accordance  with  the 
usual 6  methods,  and  gave  the  results  tabulated  in  the  following  table : 

B.  angustifolia.  B.  purpurea. 

Moisture    10.90  10.18 

Starch    Absent  Absent 

Pentosans    15.6     15. 1  15.6 

Crude  Fiber   2477,  24.46  29.65,  29.51 

Protein    6.54,    6.96  5.31,  5-17 

Ash   7-76  6.93 

The  residues  left  after  extracting  with  alcohol  were  next  digested 
with  cold  water,  for  the  purpose  of  ascertaining  if  any  dextrin-like 
substances  were  present.  The  residue  left  after  extracting  ten 
grammes  of  the  root  of  B.  angustifolia  with  alcohol,  when  digested 
with  cold  water  yielded  considerable  soluble  material.  The  aqueous  ex- 
tract was  quantitatively  made  to  a  volume  of  20  ex.  (2  c.c.  =  1.0 
gramme  root).  Four  cubic  centimetres  of  this  was  diluted  to  50  c.c, 
and  25  c.c.  of  this  solution  showed  no  reducing  action  on  Fehling's 
solution.  The  other  25  c.c.  was  hydrolyzed  with  hydrochloric  acid, 
whereupon  it  showed  the  presence  of  0.0682  Gm.  lasvulose,  equiv- 
alent to  6.14  per  cent,  of  "  inuloidTike  "  material. 

The  remainder  of  the  original  aqueous  solution  (16  c.c.)  was 
made  up  to  a  volume  of  18  c.c.  with  lead  subacetate.  A  heavy  precip- 
itate was  removed  by  filtration.  This  filtrate  then  has  a  concentra- 
tion of  0.4445  Gm.  of  the  root  per  cubic  centimetre.  It  showed  a 
rotation  of  -  2.3 °,  Ventzke  in  a  1  dcm.  tube.  Assuming  a  specific  rota- 


°U.  S.  Dept.  Agr.  Bur.  of  Chem.  Bull.  107  (Revised). 


Am.  Jour.  Pharm. 
October,  1914. 


Analyses  of  Two  Echinacea  Roots. 


453 


tion  of  -32.460,  which  is  that  recorded  7  for  "  sinistrin,"  this  would 
represent  5.55  per  cent,  of  the  plant.  The  solution,  freed  from  lead 
and  hydrolyzed,  showed  the  presence  of  a  quantity  of  lsevulose  equiv- 
alent to  5.94  per  cent.  "  inuloid-like  material,"  indicating  the  non- 
carbohydrate  nature  of  the  lead  subacetate  precipitate. 

Inulin  was  determined  by  the  method  of  DragendorfT  8  wherein 
the  plant  is  extracted  with  water  55 0  to  60  0  and  the  inulin  precip- 
itated with  three  volumes  of  alcohol.  The  inulin  was  determined  by 
determining  the  lsevulose  formed  when  this  precipitate  was  hy- 
drolyzed. A  correction  of  0.1  gm.  per  100  c.c.  of  the  volume  of  the 
filtrate  was  made  for  the  solubility  of  the  inulin.  Whether  or  not 
this  inulin  precipitate  included  any  of  the  material  determined  as 
"  inuloid  "  was  not  established.  The  following  table  gives  the  results 
of  the  various  estimations  of  alcohol  insoluble  carbohydrates  : 


Determination  of  the  Alcohol  Soluble  Carbohydrates  by  Polari- 
se 0  pic  methods. — One  hundred  grammes  of  B.  angustifolia  were  com- 
pletely extracted  with  hot  alcohol.  The  combined  alcoholic  extracts 
were  concentrated  under  diminished  pressure  to  a  volume  of  200  c.c. 
An  aliquot  of  this  solution,  equivalent  to  74  grammes  of  the  root, 
after  the  complete  removal  of  the  alcohol,  was  taken  up  in  water, 
clarified  with  an  excess  of  lead  subacetate,  and  made  up  to  a  volume 
of  100  c.c.  This  solution  showed  a  rotation  of  -  2.20  in  a  2  dcm.  tube 
at  220  C. 

Fifty  cubic  centimetres  of  the  filtrate  from  the  lead  subacetate 
precipitation  was  freed  from  the  lead  and  inverted  by  standing  with 
5  c.c.  hydrochloric  acid  for  24  hours.  The  solution  was  neutralized 
and  made  up  to  100  c.c.  It  showed  a  rotation  of  -  13.250  in  a 
2  dcm.  tube  at  220  C,  and  of  -  6.8°  at  86°  C.  in  a  2  dcm.  tube.  These 
readings  are  on  the  Ventzke  scale. 

Converting  these  readings  to  the  calculated  rotations  of  a  normal 
solution  (26  Gm.  in  100  c.c),  we  have:  direct  reading  at  220  C.  of 
-0.770  ;  invert  at  220  C.  of  -9.310  ;  and  invert  reading  at  86.°  C. 
of  -  4.780.  The  percentage  of  sucrose  calculated  by  Clerget's  formula 

7  DragendorfT,  "  Plant  Analysis,"  p.  67. 

8  "  Plant  Analysis,"  p.  87. 

9  "  Biochem.  Handlexikon,"  2,  189. 


B.  angustifolia. 


B.  purpurea. 

not  determined 
9.16% 


Inulin 
Inuloid' 


5-9% 
5.94,  6.14% 


454 


Analyses  of  Two  Echinacea  Roots. 


<  Am.  Jour.  Pharm. 
\     October,  1914. 


is  6.5  per  cent.  The  percentage  of  lsevulose  calculated  on  the  basis  of 
the  change  in  rotation  of  the  inverted  solution  due  to  change  in 
temperature  is  3.99  per  cent.10 

The  following  table  includes  the  results  of  the  quantitative  work 
carried  out  upon  the  alcohol  extract,  which  was  examined  for  sucrose 
and  hexose  sugars,  and  for  resin  (insoluble  in  water)  : 

B.  angustifolia.  B.  purpurea. 

Resin    1.84  2.00 

Sucrose    6.92  340 

Reducing  sugars    3.65,  3-52,  3.80  341 

The  roots  were  examined  for  alkaloids.  Of  each  species  we  used 
duplicate  ten-gramme  samples  for  assay.  When  examined  by  the 
method  which  is  official  for  belladonna  root,11  residues  were  obtained 
from  B.  angustifolia  weighing  0.0054  and  0.0077  gramme.  From 
B.  purpurea  the  weights  found  were  0.0086  and  0.0063  gramme. 
These  residues  were  not  alkaloidal,  as  they  failed  to  neutralize  any 
N/50  acid,  and^the  slightly  acid  solutions  gave  no  precipitate  with 
Mayer's  reagent. 

In  order  to  affirm  this  point  200  grammes  of  Brauneria  angusti- 
folia were  exhausted  with  Prollius' 12  solution  by  percolation.  The 
percolate  was  thoroughly  extracted  with  several  portions  of  dilute  sul- 
phuric acid,  and  from  this  acid  solution  we  were  able  to  obtain  neither 
an  alkaloidal  extract  nor  even  a  precipitation  test  with  Mayer's  re- 
agent. We  conclude,  therefore,  that  no  alkaloid  sufficiently  basic  to  be 
extracted  by  the  ordinary  methods  is  present  in  this  drug.  This,  how- 
ever, does  not  exclude  the  possibility  of  the  presence  of  choline  or 
allied  substances.  The  recent  work  of  Power  and  Browning13  in 
isolating  choline  from  dandelion  root  makes  this  a  possibility  worthy 
of  note.  Brauneria  purpurea  was  not  further  studied  in  this  connec- 
tion. 

Volatile  Oil  in  B.  angustifolia. — A  portion  of  the  fresh  roots 
equivalent  to  3.7  kilogrammes  air  dried  was  distilled  with  steam  until 
the  distillate  was  free  from  volatile  oil.  The  first  runnings  were  very 
slightly  turbid  and  carried  the  odor  characteristic  of  the  drug.  The 

10 "  Commercial  Organic  Analysis,"  Allen,  vol.  1,  p.  356  (1908).  The 
observed  rotations  of  the  normal  solution  are  about  1.50  to  the  left  greater 
than  those  calculated  for  a  mixture  of  lsevulose  and  sucrose. 

11  U.  S.  Disp.,  19th  Ed.,  p.  228. 

12  Alcohol  8  cc,  ether  88  c.c,  ammonia  (10  per  cent.)  4  c.c. 
13 /.  Chem.  Soc,  101,  241 1  (1912). 


Am.  Jour.  Pharm.  \ 
October,  1914.  j 


Analyses  of  Tzvo  Echinacea  Roots. 


455 


oil  separated  in  the  usual  manner  weighed  1.4  Gm.  It  was  amber 
colored  and  had  a  powerful  odor.  This  is  equivalent  to  0.04  per 
cent,  of  the  air-dried  drug. 

The  resin,  to  which  the  medicinal  properties  are  ascribed,  was 
prepared  from  a  quantity  of  the  fresh  drug,  corresponding  to  33.3 
kilogrammes  of  air-dried  drug.  This  drug  was  exhausted  by  per- 
colation with  alcohol,  the  percolate  (260  litres)  was  concentrated  by 
distillation  under  diminished  pressure  to  a  volume  of  1 1.5  litres.  This 
concentrated  alcoholic  solution,  from  which  a  fatty  layer  separated 
in  considerable  quantity,  was  mixed  with  about  20  litres  of  distilled 
water,  whereupon  the  precipitation  of  the  resin  was  complete.  After 
continued  agitation  for  the  purpose  of  thoroughly  washing  the  resin, 
and  long  standing,  the  resin  separated  above  a  clear,  reddish-brown 
aqueous  layer.  By  siphoning,  most  of  the  aqueous  layer  could  be 
separated  from  the  resin.  It  was  noticed  that  a  very  slight  inter- 
mediate zone  between  the  resin  layer  and  the  aqueous  layer  con- 
tained crystalline  material.  This  was  separated  by  mechanical 
means  and  in  very  small  quantity,  and  crystallized  from  95  per  cent, 
alcohol.  It  proved  to  be  an  impure  phytosterol,  crystallizing  in  the 
characteristic  laminae,  melting  at  about  131 0  to  1360  indefinitely,  and 
giving  the  usual  color  reactions.   It  was  returned  to  the  resin. 

The  resin  was  finally  washed  with  water,  taken  up  in  alcohol, 
and  then  dried  in  a  vacuum.  The  weight  was  628  Gm.,  equivalent  to 
1.88  per  cent.  It  is  a  brownish-yellow  resin,  and  if  dissolved  in 
alcohol  forms  an  amber-colored  solution,  which  yields  no  crystalline 
deposit.  It  is  possible,  however,  to  obtain  in  the  first  fraction  a  green 
resinous  deposit,  which  differs  from  the  resin  proper,  which  has  the 
characteristic  taste  of  the  root.  The  material  was  brought  into  one 
fraction,  taken  up  in  purified  sawdust,  and  extracted  with  the  follow- 
ing results : 

Gramme. 


Ligroin  extract    222.0 

Ether  extract   107.0 

Chloroform  extract   180.0 

Ethyl  acetate  extract    35.0 

Alcohol  extract    70.0 


Total    614.0 


We  are  studying  these  extracts  as  well  as  the  water-soluble  ex- 
tract in  more  detail. 

Chemical  Research  Laboratory,  The  Upjohn  Company, 
Kalamazoo,  Michigan. 


456  Proposed  U.  S.  P.  IX  Limitations.    {Am0;tJ0°bl£;  g£" 


PROPOSED  U.  S.  P.  IX  LIMITATIONS  FOR  THE  ASH  CON- 
TENT OF  DRUGS. 

By  M.  I.  Wilbert,  Washington,  D.  C. 

The  figures  given  in  the  second  instalment  of  abstracts  of  pro- 
posed new  descriptions  and  standards  for  the  drugs  of  vegetable 
and  animal  origin  to  be  included  in  the  U.  S.  P.  IX  (/.  Am.  Pharm. 
Assoc.,  1914,  vol.  3,  pp.  359-416)  suggest  a  comparison  with  other 
available  data  as  a  basis  for  comment  and  criticism.  Among  the  newer 
pharmacopoeias  the  German,  Austrian,  Swiss,  and  Dutch  appear  to 
include  ash  limitations  more  frequently  than  do  any  of  the  cor- 
responding books  of  other  countries,  and  these  four  books  have  been 
selected  as  being  fairly  representative  of  the  general  requirements 
made  in  European  pharmacopoeias. 

The  quotations  designated  "  recent  literature  "  are  compilations 
of  the  maximum  and  minimum  figures  given  by  various  authors  re- 
ferred to  in  recent  numbers  of  the  Hygienic  Laboratory  Bulletins, 
embodying  the  Digest  of  Comments  on  the  Pharmacopoeia  of  the 
United  States  of  America  and  on  the  National  Formulary,  for  the 
calendar  years  1909  to  191 2,  inclusive.  These  figures  suffice  to  in- 
dicate the  probable  extremes  of  the  ash  content  of  drugs  found  in 
commerce  at  the  present  time,  and  reflect  actual  conditions  so  far  as 
these  have  been  reported. 

A  casual  survey  of  the  figures  presented  in  the  appended  table 
suggests  that  a  few  of  the  root  drugs,  like  apocynum,  cimicifuga, 
pyrethrum,  and  spigelia,  are  not  sufficiently  well  known  abroad  to 
warrant  their  recognition.  Other  drugs,  like  sweet  almonds,  physo- 
stigma,  musk,  and  vanilla,  do  not  appear  to  vary  sufficiently  to  justify 
systematic  records  being  made  of  their  ash  content,  or,  as  in  the  case 
of  musk,  more  particularly,  are  so  expensive  that  the  determination 
of  the  ash  content  is  not  generally  adopted  as  a  means  of  determining 
the  purity  or  quality  of  the  drug. 

Among  the  figures  that  may  be  considered  as  being  comparatively 
low  are  those  for  asafoetida,  ipecac,  and  vanilla.  The  first  of  these 
drugs  frequently  contains  very  much  more  foreign  matter  than  would 
be  permissible  under  the  proposed  limitations.  This  foreign  matter 
is  present  to  a  considerable  extent,  at  least,  because  of  the  methods 
employed  in  collecting  asafoetida,  and  it  is  questionable,  indeed, 


Atu.  Jour.  Pharm. 
October,  1914. 


J    Proposed  U.  S.  P.  IX  Limitations.  457 


whether  the  inclusion  of  earthly  impurities  is  not  preferable  to  the 
now  frequently  practised  adulteration  or  even  substitution  of  asa- 
fcetida  by  other  gum  resins  which,  while  they  serve  to  increase  the 
alcohol  soluble  material  and  reduce  the  ash  content  of  the  drug  as 
offered,  are  quite  foreign  to  and  do  not  contain  any  appreciable 
quantity  of  the  odorous  principles  found  in  true  asafcetida. 

The  maximum  ash  content  permitted  for  ipecac  appears  to  be 
somewhat  low,  certainly  lower  than  is  the  maximum  recognized  in 
other  pharmacopoeias.  The  same  is  true  of  vanilla,  and  in  connection 
with  this  drug  there  is  some  question  as  to  whether  the  ash  content 
limitation  for  the  whole  drug  is  really  of  value  or  is  necessary. 

The  drugs  for  which  the  ash 'content  limitation  appears  to  be 
rather  high  are  much  more  numerous  and  include  aloes,  cantharides, 
belladonna  leaves,  colocynth,  coriander,  gambir,  glycyrrhiza,  guaiac, 
linseed,  lupulin,  myrrh,  squills,  mustard,  stramonium,  strophantus,  ta- 
raxacum, valerian,  and  ginger.  • 

A  comparison  of  the  proposed  limitation  for  the  ash  of  aloes  with 
the  limitations  found  in  foreign  pharmacopoeias  suggests  the  possible 
intent  of  providing  for  the  rather  inferior  Asiatic  or  Moka  aloes 
usually  sold  as  Socotrine  aloes,  which  has  been  found  to  contain 
rather  large  quantities  of  foreign  material.  A  reasonably  pure  in- 
spissated juice  of  the  aloe  plant  when  prepared  in  a  cleanly  method 
should  readily  comply  with  the  requirements  made  in  the  German, 
Swiss,  and  Netherlands  pharmacopoeias. 

The  ash  content  for  cantharides,  while  it  agrees  with  the  limita- 
tions included  in  the  Dutch  pharmacopoeia,  is,  nevertheless,  higher 
than  need  be.  A  number  of  careful  investigators  have  asserted  that 
a  drug  of  good  quality  should  contain  less  than  eight  per  cent,  of  ash. 

The  proposition  to  permit  20  per  cent,  of  ash  in  belladonna  leaves 
appears  to  be  inordinately  liberal  when  compared  with  the  limitation 
of  10  per  cent,  of  ash  for  digitalis.  Belladonna  has  a  comparatively 
smooth  leaf  that  would  hold  little  or  no  sand  or  dust,  while  the  dig- 
italis leaf,  being  hairy,  is  much  more  readily  contaminated  by,  and 
is  more  difficult  to  rid  of,  adhering  sand  and  dirt.  The  figures 
reported  in  literature  also  suggest  the  desirability  of  some  additional 
leeway  for  digitalis  and  the  lack  of  any  serious  need  for  so  high  an 
ash  content  for  belladonna  leaf. 

Colocynth  is  another  drug  that  appears  to  have  been  given  a 
rather  high  limit  and  one  for  which  a  minimum  requirement  of  ash 
might  be  considered  in  view  of  the  fact  that  the  seed  of  colocynth  has 


458  Proposed  U.  S.  P.  IX  Limitations.     {AmoJoZ-' \9um' 

been  found  to  contain,  on  the  average,  much  less  ash  than  does  the 
pulp. 

Gambir  varies  considerably  in  its  composition,  and,  being  an  ex- 
tract, is  not  infrequently  contaminated  by  the  deliberate  addition  of 
sand  and  dirt.  A  number  of  observers  in  this  country  have  stated  that 
6  per  cent,  of  ash  should  not  be  exceeded  by  a  drug  of  good  quality, 
and  this  would  in  a  general  way  conform  with  the  limitations  made 
for  the  closely  related  drug,  catechu,  in  foreign  pharmacopoeias. 

Lupulin  is  another  drug  that  has  rather  a  liberal  allowance  for 
ash,  and,  while  it  is  true  that  the  maximum  permitted  in  Austria  and 
Switzerland  is  usually  exceeded  by  the  commercially  available  prod- 
uct, it  has,  nevertheless,  been  repeatedly  shown  that  commercial 
lupulin  can  readily  be  freed  from  contaminating  sand  and  dirt  to  such 
and  extent  as  to  bring  it  below  the  10  per  cent,  limit  for  ash,  and  that 
absolutely  pure  lupulin  obtained  directly  from  the  strobiles  of  the 
hop  will  comply  with  the  Dutch  pharmacopceial  limitation  of  6  per 
cent. 

The  proposed  ash  content  for  squill,  while  it  agrees  with  the 
maximum  permitted  in  the  Austrian  pharmacopoeia,  appears  to  be 
unnecessarily  high,  when  one  considers  the  nature  of  the  drug  and  the 
lack  of  need  for  providing  for  inorganic  impurities. 

The  ash  content  limitations  for  the  several  seeds,  like  anise  and 
fennel,  while  in  accord  with  the  limitations  set  in  foreign  pharma- 
copoeias, are  generally  higher  than  the  figures  included  in  a  recent 
regulation  promulgated  by  the  Bureau  of  Chemistry  for  these  drugs 
when  entered  for  imports. 

The  proposition  to  include  limitations  for  ash  insoluble  in  diluted 
hydrochloric  acid,  in  connection  with  the  several  spices  and  with 
senna,  while  thoroughly  well  established  in  the  trade,  is  rather  a 
novel  one  in  pharmacopoeial  work,  and  there  may  be  considerable  dif- 
ference of  opinion  as  to  the  desirability  of  including  such  an  addi- 
tional complicating  requirement  at  this  time. 

Taken  as  a  whole,  it  must  be  said  that  the  proposed  limitations  for 
ash,  while  many,  are  reasonably  conservative  and  comply  fairly  well 
with  conditions  as  they  exist  in  the  drug  market  at  the  present  time. 
Some  further  comparative  study  of  the  requirements,  however,  should 
prove  interesting  and  will  no  doubt  lead  to  the  revision  of  the  figures 
in  connection  with  at  least  a  few  of  the  drugs  referred  to. 


^cfXr'Jgw"11'}    Proposed  U.  S.  P.  IX  Limitations.  459 

Table  Showing  Proposed  U.  S.  P.  Limitations  for  Ash  Compared  with  Re- 
quirements Included  in  the  German,  Austrian,  Swiss,  and  Nether- 
lands Pharmacopoeias,  and  the  Variations  Reported  in  Recent 
Literature. 


U.  S.  P.  IX. 

German 

V 

Austrian 
VIII 

Helvetian  Netherlands 
IV  IV 

Recent 
literature 

4 

5 

3 

4 

4 

I.23-  364 

6 

6 

3-0  ~  0. 

Agar-agar   

5 

2.6  -  4. 

Aloe   

4 

1-5 

1 

i.5 

1.5 

0.65-  5.65 

8 

0 

6 

3-7 

4-6  -  7.3i 

4 

0-5 

1 

0.5 

1 

0.05-  0.27 

10 

10 

IO 

10 

5.6  -18.46 

9 

3-4 

9 

8 

6.2  -11.5 

15 

15 

10 

20 

10 

5-  -6370 

3 

3 

2.2  -  5.44 

Aurantii  Amari  Cortex 

7 

6 

7 

37  -  5-5 

Belladonnas  Folia  .... 

20 

15 

15 

2.35-23.5 

Belladonnas  Radix   

7 

0 

7 

6.07-  7.84 

2 

2 

2 

1-5 

2 

1.2  -  3.8 

4 

4.2  -  5.80 

Calumba   

8 

6 

8 

4.O      -  0.2 

2 

0.5  -IO.O 

Cannabis   

15 

15 

6.0  -I4.44 

9 

8 

8 

9 

6.5  -I0.29 

1* 

6.5 

6.5 

6.5 

4-3  -  6.6 

Cardamomi  Semen  .... 

8 

10 

8 

8 

37  -  92 

8 

7 

8 

5.  -11.9 

0.5* 

8 

8 

7 

6 

5-4  -  7.3 

10 

4.87-  9.65 

Cinnamomum  Saigon- 

icum   

2* 

5 

5 

8 

1.30-  5.6 

Cinnamomum  Zeylan- 

2* 

5 

5 

3-3  -  6.83 

6 

6 

3.28-  9-4t 

Colchici  Semen   

8 

8 

2.4  -  3-5 

15 

7 

3.60-13.03 

12 

5.26-16.71 

7-5 

7 

4.55-  8.10 

8 

8 

8 

10 

10 

10 

10 

4.6  -18.5 

5 

5 

5 

2.6  -  4.3 

10 

10 

10 

10 

7-  -2375 

6 

5 

37  -  6.5 

*Ash  insoluble  in  diluted  hydrochloric  acid. 


460  Proposed  U.  S.  P.  IX  Limitations.     { A^ctJ0°buerr;  gj*- 


U.  S.  P.  IX.  German 
V 

Austrian 
VIII 

Helvetian  Netherlands  Recent 
IV             IV  literature 

Gambir  (Catechu)  . 

...  9 

6 

5 

5  5 

3.03-32.0 

,  . .  6 

5 

6  2-6 

2.5  -  542 

...  7 

6 

6  6 

4.4  -  8.96 

. . .  16 

10 

15.5  15 

3.63-16.60 

...  ■  4 

1 

1.5 

1. 63-1 1.7 

8 

9.70-10.13 

...30 

24 

20 

17.39-31.54 

. . .  1.8-4.5 

6 

1.8-4  1.8-6 

2.83-  9.34 

Jalapa   

. . .  6.5 

6-5 

5 

6.5 

3-2  -  7-55 

2 

1.47-  5.9 

•••  5 

5 

1.4  -  446 

.  ,  ,  10 

10 

4.91-  6.9 

6 

5 

5 

5 

3.3  -  5.85 

. .  8 

8 

5.1  -11.65 

.  ,  16 

10 

10  0 

6.60-38.25 

•  •  •  3 

3 

3 

3  5 

1.   -  4.10 

...13 

13 

12.4  -14.8 

...  8 

8 

5 

3 

5 

1.23-  3-3 

...  8.5 

7 

6 

6  5 

4.1  -15.65 

Nux  Vomica  

...  3-5 

3 

3-5  3 

1.25-  3.62 

....  7 

0.12*-  8.3 

2* 

5 

.••  3 

3-6  -  5.36 

•  ••  5 

4-7  -  7-5 

Rhamnus  Purshiana 

...  8 

6 

10 

4.14-  8.7 

...  13 

12 

12 

13 

7.1  -12.12 

Santalum  Rubrum  . . 

...  3 

5 

8 

3-6  -34.57 

27.85-13-38 

Scilla   

8 

5 

8 

5 

1.8  -  4.2 

....  5 

5 

2.6  -  5-7 

12 

12 

10 

10  6-8 

8.2  -14.32 

...  3* 

5 

5  8 

5.2  -  8.06 

7.93-40.81 

Stillingia   

•  ••  5 

5.42-  6.85 

20 

20 

5.8  -22.16 

• .  •  5 

5 

3-°  4.o 

.  .  10 

8 

5.42-14.8 

...  3-5 

3-5 

3-5  3-5 

1.88-29. 

•  ••  3 

3 

0.96-  3.31 

Uva  Ursi   

4 

2.1  -  7.01 

...  20 

10 

12 

6.8  -32.73 

6 

10 

12 

..  8 

7 

5 

7  8 

3.I0-*  7.9 

*  Ash  insoluble  in  diluted  hydrochloric  acid. 


AnoctJrer  ^9i4m'l  Estimation  of  Morphine  and  Lloyd's  Reagent.  461 


NOTES  ON  THE  ESTIMATION  OF  MORPHINE  AND  ON 
LLOYD'S  REAGENT.1 

By  H.  M.  GoRDiN  and  J.  Kaplan. 

1.  Attempt  to  shake  out  morphine  with  a  mixture  of  alcohol  and 
chloroform  from  a  saturated  solution  of  potassium  carbonate. 

When  a  saturated  solution  of  potassium  carbonate  is  shaken  with 
alcohol  or  a  mixture  of  equal  volumes  of  alcohol  and  chloroform,  most 
of  the  alcoholic  solvent  very  quickly  separates  out  on  the  surface  of 
the  heavier  aqueous  layer.  This  was  proved  by  adding  a  definite 
volume  of  the  alcoholic  liquid  to  an  equal  volume  of  the  saturated 
solution  of  potassium  carbonate,  shaking  the  mixture  vigorously,  and 
reading  off  the  volume  of  the  upper  layer  after  the  liquid  has  sepa- 
rated in  two  layers.  In  all  cases  the  volume  of  the  alcoholic  layer 
was  only  a  little  less  than  the  volume  of  the  alcoholic  liquid  originally 
taken. 

Owing  to  there  being  no  good  immiscible  solvent  for  the  extrac- 
tion of  morphine  from  the  solution  of  its  salts  in  water,  an  attempt 
was  made  to  saturate  such  a  solution  with  potassium  carbonate  and 
to  use  a  mixture  of  equal  volumes  of  alcohol  and  chloroform  as  im- 
miscible solvent.  The  aqueous  liquid,  after  being  shaken  once  with 
an  equal  volume  of  the  alcoholic  liquid,  using  about  40  c.c.  of  each 
for  about  0.1  g.  of  morphine  in  the  form  of  salt,  gave  no  test,  in 
acidified  solution,  with  Mayer's  or  Wagner's  reagent,  while,  on  the 
other  hand,  the  alcoholic  liquid  was  found  to  contain,  besides  mor- 
phine, small  amounts  of  potassium  carbonate,  together  with  small 
amounts  of  other  substances,  coming  either  from  impurities  in  the 
carbonate,  or  from  a  partial  decomposition  of  morphine  by  the  latter, 
or  from  both  sources.  Even  when  the  potassium  carbonate  was  pre- 
viously washed  with  alcohol  and  dried,  the  alcoholic  solution  of  the 
morphine  contained  small  amounts  of  other  substances. 

It  was  thought  that  by  washing  the  residue  left  after  distilling 
off  the  alcoholic  liquid  from  the  morphine  with  a  saturated  solution 
of  the  alkaloid  the  impurities  could  be  eliminated  so  that  the  morphine 
could  be  determined  alkalimetrically.  For  this  purpose  definite 
amounts  of  morphine  were  dissolved  in  acidified  water,  the  solution 


1  Read  at  the  Detroit  meeting  of  the  American  Pharmaceutical  Associa- 
tion, 1914. 


462    Estimation  of  Morphine  and  Lloyd's  Reagent.  {A^tJX.rr"  Kf*' 

saturated  with  potassium  carbonate,  either  ordinary  or  previously 
washed  with  alcohol,  and  then  shaken  with  a  definite  volume  of  equal 
volumes  of  a  mixture  of  alcohol  and  chloroform.  After  complete 
separation  of  the  liquid  into  two  layers,  an  aliquot  portion  of  the 
alcoholic  layer  was  drawn  off  and  evaporated  to  dryness.  The  residue 
was  washed  with  a  saturated  solution  of  morphine  in  water  until  the 
washings  gave  no  test  for  potassium  carbonate  with  phenolphthalein, 
and  the  morphine  determined  alkalimetrically,  using  N/25  H2S04 
and  N/50  KOH.   The  indicator  was  methyl-red. 

The  experiments  showed  that  in  all  cases  the  amount  of  morphine 
found  exceeded  the  amount  originally  taken,  the  variation  being  from 
2  to  15  per  cent.  Hence  the  method,  at  least  in  the  form  here  de- 
scribed, is  not  reliable. 

2.  Extraction  of  alkaloids  by  means  of  Lloyd's  reagent. 

Owing  to  the  facility  and  completeness  of  precipitation  of  al- 
kaloids by  Lloyd's  reagent,  it  was  thought  that  this  reagent  could  be 
advantageously  used  for  the  quantitative  extraction  of  alkaloids  from 
their  original  sources  or,  in  general,  from  the  solution  of  their  salts 
in  water. 

It  is  evident  that  in  order  to  attain  this  aim  it  is  necessary  to 
prove  that  the  alkaloids,  once  precipitated  by  Lloyd's  reagent,  can  be 
readily  and  completely  recovered  from  the  precipitate  containing 
alkaloid  and  reagent.  With  a  view  of  determining  this  point,  the 
following  experiments  were  carried  out : 

A  definite  amount  of  morphine  was  dissolved  in  an  excess  of 
dilute  sulfuric  acid,  the  alkaloid  completely  precipitated  with  an  ex- 
cess of  Lloyd's  reagent,  and  the  precipitate  washed  with  water  till  the 
washings  gave  no  test  for  sulfuric  acid.  The  precipitate  was  dried 
at  6o°  and  then  repeatedly  extracted  with  boiling  methyl  alcohol, 
which  is  a  very  fair  solvent  for  morphine.  The  solvent  was  evapo- 
rated to  dryness,  and  the  residue  weighed.  This  residue  was  free 
of  sulfuric  acid,  showing  it  to  be  probably  free  morphine,  but  its 
amount  was  less  than  4  per  cent,  of  the  morphine  originally  taken. 

The  precipitate  was  then  again  extracted  with  methyl  alcohol  to 
which  a  small  amount  of  ammonia  had  been  added,  and  the  residue 
left  after  again  evaporating  the  solvent  weighed.  The  total  amount 
of  alkaloid  recovered  by  the  two  successive  extractions  was  about  90 
per  cent,  of  the  morphine  taken. 

Another  experiment  was  made  with  strychnine,  using  chloroform, 
which  is  an  exceptionally  good  solvent  for  this  alkaloid.    A  dilute 


Anoctober  i9i4rm"}  Estimation  of  Morphine  and  Lloyd's  Reagent.  463 

solution  of  strychnine  in  water  acidified  with  sulfuric  acid  was  com- 
pletely precipitated  with  an  excess  of  Lloyd's  reagent,  and  the  pre- 
cipitate, after  thorough  washing  with  water,  dried  at  6o°.  A  portion 
of  the  precipitate  containing  about  0.2  g.  of  strychnine  was  sus- 
pended in  a  little  water  containing  an  excess  of  ammonia,  and  then 
repeatedly  shaken  out  with  successive  portions  of  chloroform,  using 
20  c.c.  of  the  latter  for  the  first  shaking  and  15  c.c.  each  time  after- 
wards. It  was  found  that  even  after  ten  consecutive  operations  the 
chloroform  did  not  ,  remove  all  of  the  alkaloid,  as  was  shown  by 
evaporating  some  of  the  chloroformic  extract  to  dryness,  taking  up 
the  residue  with  acidified  water,  and  testing  the  resulting  solution 
with  Mayer's  and  Wagner's  reagents,  both  of  which  continued  to 
give  a  heavy  precipitate.  Hence  by  this  method  it  is  extremely  dif- 
ficult quantitatively  to  recover  the  strychnine  from  a  solution  of  its 
salts  in  water.  Whether  other  methods  would  be  more  successful 
will  have  to  be  determined  by  further  experimentation. 

3.  Attempt  to  facilitate  the  removal  of  strychnine  from  the  pre- 
cipitate obtained  by  adding  Lloyd's  reagent  to  a  solution  of  a  salt  of 
the  alkaloid  in  water. 

The  precipitate  obtained  by  adding  an  excess  of  Lloyd's  reagent 
to  an  aqueous  solution  of  a  salt  of  strychnine  is  almost  perfectly 
tasteless,  though  it  contains  all  of  the  alkaloid  of  the  original  solu- 
tion. This  seems  to  suggest  the  veiw  that  the  reagent  forms  with 
the  alkaloid  an  exceptionally  stable  combination,  and  this  view  is 
further  strengthened  by  the  fact  that,  as  was  shown  above,  it  is  ex- 
tremely difficult  completely  to  recover  the  alkaloid  from  the  pre- 
cipitate. 

On  the  other  hand,  as  will  be  reported  later  by  Dr.  McGuigan,  the 
precipitate  acts  physiologically  very  much  like  strychnine  diluted 
with  an  inactive  substance,  showing  that  in  the  living  digestive  ap- 
paratus the  union  of  alkaloid  and  reagent  is  readily  disrupted.  Since 
it  was  reasonable  to  ascribe  this  disrupting  effect  to  the  digestive 
enzymes  of  the  animal  body,  experiments  were  made  in  order  to  de- 
termine whether  some  of  these  enzymes  would  show  the  same  dis- 
rupting effect  in  vitro.  If  this  were  so,  dilute  hydrochloric  acid  in 
presence  of  pepsin,  or  chloroform  in  presence  of  alkali  and  either 
ptyalin  or  trypsin,  readily  ought  to  extract  the  strychnine  from  the 
precipitate.  The  following  experiments  were,  therefore,  carried  out 
with  these  enzymes : 

Pepsin. — The  thoroughly  washed  and  dried  precipitate  obtained 


464  62nd  Annual  Meeting  of  the  A.  P.  A.  {A™-ctJ0™r  SSf** 

by  adding  an  excess  of  Lloyd's  reagent  to  an  aqueous  solution  of 
strychnine  sulfate  was  digested  with  very  dilute  hydrochloric  acid 
containing  a  little  pepsin,  shaking  the  mixture  for  an  hour  and  then 
filtering.  The  filtrate  was  tested  with  Mayer's  and  Wagner's  re- 
agents. Neither  of  these  gave  any  indication  of  the  presence  of  an 
alkaloid.  Hence  in  zntro  pepsin  has  no  disrupting  effect  on  the  pre- 
cipitate. 

Ptyalin  and  Trypsin. — The  precipitate  was  suspended  in  a  very 
dilute  solution  of  ammonia  containing  either  ptyalin  or  trypsin,  and 
the  mixture  repeatedly  shaken  out  with  chloroform.  It  was  found 
that  even  after  ten  successive  treatments  with  chloroform  the  pre- 
cipitate still  retained  some  of  the  strychnine.  Hence  these  enzymes, 
too,  have  no  disrupting  effect  on  the  precipitate. 

Northwestern  University  Schools  of  Pharmacy  and  Dentistry. 


THE  SIXTY-SECOND  ANNUAL  MEETING  OF  THE  AMER- 
ICAN PHARMACEUTICAL  ASSOCIATION. 

The  1914  meeting  of  the  American  Pharmaceutical  Association 
was  held  in  the  city  of  Detroit  during  the  week  of  August  24-29,  1914, 
and  was,  in  fact,  a  joint  meeting  of  that  Association  with  the  Michi- 
gan State  Pharmaceutical  Association,  the  Michigan  Pharmaceutical 
Travelers'  Association,  the  Conference  of  Pharmaceutical  Faculties 
and  the  National  Association  of  Boards  of  Pharmacy.  More  than 
800  persons  were  registered,  and  the  sessions  of  the  several  associa- 
tions enumerated  and  also  the  scientific  meetings  of  the  several 
sections  of  the  American  Pharmaceutical  Association  were  very 
well  attended.  It  was  not  unusual  to  have  four,  and  even  five,  ses- 
sions going  on  at  the  same  time,  so  that  it  would  be  practically  im- 
possible for  any  one  person  to  reflect  the  proceedings  even  in  part, 
and  in  this  report  nothing  more  ambitious  will  be  attempted  than  to 
try  and  reflect  in  outline  the  happenings  of  the  week  as  they  appealed 
to  an  interested  participant. 

The  first  general  session  of  the  Association  was  called  to  order  by 
President  George  M.  Beringer  on  the  afternoon  of  August  24th.  The 
local  committee  had  very  considerately  neglected  to  provide  the 
usual  addresses  of  welcome,  so  that,  contrary  to  established  pre- 


^'obSSftSST"'}  62nd  Annual  Meeting  of  the  A.  P.  A.  465 

cedent,  the  proceedings  were  inaugurated  by  the  reading  of  the 
President's  address. 

The  address  presented  this  year  was  an  unusually  comprehensive 
communication  that  touched  on  many  important  features  of  associa- 
tion work  and  embodied  a  number  of  recommendations  that  should 
contribute  materially  to  make  for  real  progress  in  true  pharmacy. 
The  address  was  listened;  to  attentively  by  all  of  the  members  present, 
and  was  subsequently  referred  to  a  committee  of  five  to  report  at  a 
later  session. 

Following  the  reading  of  the  address  of  the  president,  a  number 
of  representatives  and  delegates  were  requested  to  present  felicita- 
tions or  reports,  and  these  addresses,  with  the  usual  recess  for  the 
selection  of  members  of  the  nominating  committee,  served  to  extend 
the  first  general  session  to  about  the  usual  late  hour  for  adjourning. 

The  second  general  session  of  the  Association  was  devoted 
largely  to  routine  business,  including  the  presentation  of  reports  of 
the  various  committees.  The  only  item  of  business  regarding  which 
there  appeared  to  be  a  difference  of  opinion  was  the  report  of  the 
committee  on  time  and  place  of  next  meeting,  and  this  was  made  the 
special  order  of  business  at  an  extra  session  held  on  Friday  evening. 

Many  of  the  members  of  the  Association  are  interested  only  in 
the  work  of  one  or  the  other  of  the  sections,  and  these  members,  at 
least,  had  no  cause  to  be  dissatisfied. 

The  programs  of  the  several  sections  of  the  Association  included 
a  total  of  more  than  125  communications,  some  of  which  were  of 
more  than  usual  interest.  In  the  following  paragraphs  an  effort  will 
be  made  to  reflect  the  nature  of  the  programs  themselves  rather  than 
attempt  to  present  a  comprehensive  review  of  what  was  said  by  the 
individual  essayists. 

The  Section  on  Scientific  Papers,  or  "  Scientific  Section,"  as  it 
was  generally  designated  on  the  programs  for  this  year,  had,  as  usual, 
a  liberal  and  varied  selection  of  communications,  Edsel  A.  Rud- 
diman,  of  Nashville,  Tenn.,  presided,  and  Wilbur  L.  Scoville,  of 
Detroit,  served  as  secretary.  The  printed  program  contained  a  total 
of  42  titles,  including  discussions  on :  Radium,  biological  products, 
immunology,  pharmacodynamic  assay  methods,  the  assay  of  opium, 
the  manufacture  of  fluidextracts,  the  nature  of  the  menstruum  for 
official  tinctures,  the  estimation  of  calomel,  the  physical  properties  of 
volatile  oils,  the  growing  of  plant  drugs,  the  differentiation  of  true 
oil  of  wintergreen  from  synthetic  methyl  salicylate,  and  many  other 


466  62nd  Annual  Meeting  of  the  A.  P.  A.  { A^g£;  f**™- 

subjects  equally  interesting  to  the  pharmacist  who  is  at  all  desirous 
of  keeping  in  touch  with  the  progress  that  is  being  made  along  scien- 
tific lines.  The  papers  presented  this  year,  while  perhaps  not  epoch- 
making,  serve  to  reflect  progress  in  a  variety  of  lines  of  research. 

Three  sessions  were  held  and  ample  time  given  for  the  discussion 
of  the  several  communications  that  were  presented. 

At  one  of  the  sessions  of  this  section  the  scope  of  Hygienic  Labo- 
ratory Bulletins  entitled  "  Digest  of  Comments  on  the  Pharmacopoeia 
of  the  United  States  of  America  and  on  the  National  Formulary  " 
was  discussed  and  a  resolution  adopted,  the  purport  of  which  was  that 
the  Digest  of  Comments  be  continued  along  the  lines  on  which  it  has 
been  developed,  and  that,  if  possible,  future  volumes  of  the  com- 
pilation be  published  more  promptly  so  as  to  make  them  increasingly 
valuable  to  the  workers  in  scientific  pharmacy,  who  find  the  publica- 
tion useful  as  a  reference  book  on  current  literature  relating  to 
articles  included  in  the  Pharmacopoeia  and  the  National  Formulary. 

The  officers  for  the  coming  year  are :  Chairman,  Herman  Engel- 
hardt,  Baltimore ;  secretary,  William  Mansfield,  New  York. 

The  Section  on  Education  and  Legislation,  under  the  able  direc- 
tion of  Hugh  Craig,  Chicago,  as  chairman,  and  F.  H.  Freericks,  Cin- 
cinnati, as  secretary,  was  scheduled  for  three  sessions  with  a  program 
including  some  18  communications.  Legislation  and  the  need  for  en- 
forcing existing  laws  were  discussed  at  some  length.  The  chairman, 
in  his  address,  expressed  the  opinion  that  legislation  is  an  over-ex- 
ploited remedy  for  pharmacal  ills  and  that  education,  while  slower,  is 
more  promising.  He  also  called  attention  to  some  of  the  educational 
needs  of  pharmacy,  and  deplored  the  lack  of  efficient  pharmacal 
educators. 

The  report  of  the  Committee  on  National  Legislation  and  of  the 
delegates  to  the  Drug  Trade  Conference  was  followed  by  a  rather 
lively  discussion  on  legislative  matters.  The  section  subsequently 
adopted  a  resolution  endorsing  the  Harrison  anti-narcotic  measure 
in  the  form  in  which  it  passed  the  Senate,  and  urged  its  final  adoption 
into  law. 

The  officers  of  the  section  for  the  coming  year  are :  Chairman, 
F.  R.  Freericks,  Cincinnati ;  secretary,  R.  A.  Kuever,  Iowa  City. 

The  Section  on  Practical  Pharmacy  and  Dispensing,  under  the 
direction  of  the  chairman,  F.  W.  Nitardy,  Denver,  and  the  secretary, 
Cornelius  Osseward,  of  Seattle,  introduced  a  rather  novel  feature  in 
the  nature  of  experience  meetings  that,  continued  at  future  meetings, 


Am.  Jour.  Pharm. 
October,  1914. 


}  62nd  Annual  Meeting  of  the  A.  P.  A.  467 


might  well  serve  to  bring  about  an  appreciation  of  existing  conditions 
in  pharmacy  and  thus  make  for  an  unprecedented  degree  of  progress. 
The  program  for  this  section,  while  it  contained  but  a  total  of  25 
titles,  occupied  no  less  than  five  sessions,  two  of  which  were  held 
during  the  boat  ride  on  Thursday  afternoon  and  evening.  The  chair- 
man himself  presented  two  exceptionally  interesting  communications, 
one  on  the  dispensing  of  ointments  in  collapsible  tubes,  and  the 
second  on  the  preparation  of  flake  agar-agar.  P^or  the  latter  purpose 
he  recommends  moistening  the  substance  with  water,  passing  through 
an  ordinary  meat-chopper,  and  then  thoroughly  drying. 

By  far  the  greater  amount  of  time  at  three  of  the  sessions  was 
devoted  to  the  consideration  of  a  number  of  pharmaceutical  queries. 
The  answers  that  were  offered  evidenced  the  need  .for  developing 
practical  commercialism  in  pharmacy  if  pharmacists  are  to  retain  any 
of  the  business  that  should  be  theirs.  The  material  offered,  while  not 
particularly  reassuring  so  far  as  present-day  conditions  may  be  con- 
cerned, was  nevertheless  promising,  and  if  repeated,  particularly  in 
connection  with  local  branch  meetings  or  in  connection  with  actual 
demonstrations,  would  go  far  toward  bringing  about  necessary  re- 
forms in  future.  The  officers  for  the  coming  year  are :  Chairman, 
Cornelius  Osseward,  Seattle ;  associate,  D.  F.  Jones,  Watertown, 
S.  D. ;  secretary,  I.  A.  Becker,  Chicago. 

The  Section  on  Pharmacopoeias  and  Formularies  presented  a 
program  containing  12  communications  and  a  general  discussion  on 
400  or  more  new  or  modified  preparations  proposed  for  the  U.  S.  P. 
IX  and  the  N.  F.  IV.  The  section  proceedings  were  conducted  by 
E.  Fullerton  Cook,  of  Philadelphia,  and  in  the  abscence  of  the 
secretary  John  K.  Thum,  of  Philadelphia,  was  elected  to  act  as 
secretary.  In  accordance  with  a  decision  of  the  Council,  this  section 
becomes  a  sub-section  or  branch  of  the  Section  on  Practical  Phar- 
macy and  Dispensing,  as  which  the  work  so  successfully  inaugurated 
during  the  two  years  of  its  existence  as  a  distinct  section  will  no  doubt 
be  continued. 

The  Section  on  Commercial  Interests,  under  the  very  able  manage- 
ment of  Harry  B.  Mason,  of  Detroit,  who  had  been  appointed  to 
serve  as  chairman  in  place  of  Gus  Lindvall,  resigned,  devoted  two 
sessions  to  the  discussion  of  twenty  or  more  communications.  By 
far  the  greater  number  of  the  papers  on  the  program  were  matters 
relating  to  practical  pharmacy,  while  others  had  little  or  nothing  to 
do  with  pharmacy  and  were,  therefore,  not  germane  to  a  meeting 


468  62nd  Annual  Meeting  of  the  A.  P.  A .  { ^kJg*  J**™- 

that  should  make  for  progress  in  pharmacy  as  such.  The  chairman, 
in  his  address,  properly  asserted  that  the  existing  "  scorn  of  com- 
mercialism in  the  drug  business  is  the  worst  kind  of  stupidity."  It  is 
equalled,  perhaps,  only  by  that  of  "  the  old-school  pharmacist  "  who 
persists  in  speaking  of  the  "  ethical  "  pharmacist  and  of  "  ethical  " 
pharmacy.  In  concluding  his  address  the  chairman  made  the  pre- 
diction that  the  college  or  school  of  pharmacy  which  now  essays  to 
teach  its  students  the  science  of  pharmacy  will  within  the  next  50 
years  to  come  really  teach  them  how  to  run  a  drug  store.  This  pre- 
diction involves  a  degree  of  progress  in  pharmacy  that  many  persons 
would  be  pleased  to  see  brought  about  in  much  less  time  than  the  limit 
set  by  Mr.  Mason.  The  officers  of  this  section  for  the  coming  year 
are :  Chairman,  E.  H.  Thiesing,  Cincinnati ;  secretary,  M.  Stolz, 
Syracuse. 

The  Historical  Section  held  a  well-attended  session,  at  which  a 
number  of  matters  of  pharmaceutic  interest  were  discussed.  W.  C. 
Alpers,  Cleveland,  presided,  and  F.  T.  Gordon,  Philadelphia,  served 
as  secretary.  Prof.  Edward  Kremers,  in  the  course  of  a  lecture  on 
"  The  Study  of  the  History  of  Pharmacy,"  demonstrated,  by  the  ex- 
hibition of  a  number  of  lantern  slides,  that  the  subject  could  be  made 
both  interesting  and  profitable  to  pharmaceutical  students  and  might 
well  be  made  an  integral  part  of  the  pharmaceutical  curriculum.  The 
officers  of  this  section  for  the  coming  year  are :  Chairman,  F.  T. 
Gordon,  Philadelphia ;  secretary,  A.  H.  Clark,  Chicago ;  historian, 
E.  G.  Eberle,  Dallas,  Texas. 

The  meetings  of  the  Women's  Section  were  presided  over  by 
Mrs.  J.  G.  Godding.  A  number  of  interesting  papers  were  read  and 
discussed,  and  the  section  is  to  be  continued  as  heretofore.  The 
officers  elected  for  the  coming  year  are :  President,  Mrs.  John  Culley, 
Ogden,  Utah ;  secretary,  Miss  Anna  J.  Bagley,  Columbus,  Ohio. 

The  House  of  Delegates  is  reported  to  have  had  credentials  from 
261  delegates,  representing  100  organizations.  Clyde  M.  Snow, 
Chicago,  presided,  and  at  the  concluding  session  a  number  of  resolu- 
tions were  adopted  and  referred  to  the  Council  of  the  Association. 
The  officers  for  the  coming  year  are:  Chairman,  W.  S.  Richardson, 
Washington ;  secretary,  J.  Weinstein,  New  York. 

In  addition  to  the  meetings  already  referred  to,  the  National 
Association  of  Boards  of  Pharmacy  and  the  American  Conference  of 
Pharmaceutical  Faculties  each  held  a  number  of  sessions,  and  a  joint 
meeting  of  these  two  bodies  with  the  Section  on  Education  and 


A^ctJo°bTr'  uu^'j^nd  Annual  Meeting  of  the  A.  P.  A.  469 

Legislation  of  the  American  Pharmaceutical  Association  was  held 
on  the  evening  of  August  28th. 

The  Committee  of  Revision  of  the  United  States  Pharmacopoeia 
held  rather  a  prolonged  conference,  at  which  several  highly  important 
matters  were  discussed.  The  Committee  on  National  Formulary 
took  advantage  of  the  opportunity  to  conclude  the  week  by  holding 
several  protracted  meetings,  at  which  a  number  of  questions  in  con- 
nection with  the  revision  of  that  book  were  finally  decided,  so  that 
the  manuscript  may  now  go  to  the  printer. 

The  final  general  session,  while  an  unusually  long  one,  will  have 
been  well  worth  the  time  devoted  to  it  if  the  changes  that  were  pro- 
vided for  are  actually  put  into  operation  at  future  meetings.  The 
amendments  to  the  by-laws  that  were  adopted  provide  for  a 
material  concentration  of  the  work  of  the  sections,  including  the 
practical  amalgamation  of  the  Section  on  Pharmacopoeias  and  For- 
mularies with  the  Section  on  Practical  Pharmacy  and  Dispensing. 
The  work  of  other  sections  is  also  more  clearly  outlined  and  will 
obviate  any  agitation  for  additional  sections  in  the  near  future. 

The  report  of  the  Committee  on  President's  Address  aroused 
considerable  discussion,  and  some  of  the  recommendations  made  by 
the  committee  were  not  approved  of.  The  report  of  the  same  com- 
mittee on  the  recommendations  made  by  the  former  secretary  of  the 
Association,  Prof.  Jas.  H.  Beal,  was,  on  motion,  referred  to  the 
Council  with  power  to  act. 

Among  the  resolutions  approved  by  the  Association  at  this  final 
session  were : 

A  resolution  to  draft  a  bill  designed  to  reform  the  present  patent 
law  so  as  to  compel  the  manufacture  in  this  country  of  all  medicinal 
products. protected  by  patent; 

A  resolution  endorsing  the  proposition  that  graduates  in  pharmacy 
only  be  appointed  as  members  of  Boards  of  Pharmacy; 

A  resolution  endorsing  the  proposed  Congress  of  National  Drug 
and  Pharmaceutical  Associations,  the  object  of  this  resolution  being 
to  bring  about  some  form  of  correlation  in  the  work  of  the  several 
organizations ; 

A  resolution  endorsing  bills  now  pending  to  bring  about  stand- 
ardization of  prices  on  proprietary  medicines ; 

A  resolution  objecting  to  the  imposition  of  a  stamp  tax  on 
proprietary  medicine ; 


470  62nd  Annual  Meeting  of  the  A.  P.  A.  { ^jggg-  fgF+ 

A  resolution  designed  to  develop  the  production  of  botanical 
drugs  in  the  United  States ;  and 

A  resolution  commending  the  present  scope  of  the  Hygienic  Labo- 
ratory Bulletins  embodying  a  Digest  of  Comments  on  the  Pharma- 
copoeia of  the  United  States  of  America  and  on  the  National  For- 
mulary, and  asking  that,  if  practicable,  these  bulletins  be  published 
more  promptly. 

Following  the  usual  vote  of  thanks  to  the  local  committees,  and  a 
special  vote  for  the  local  secretary,  the  officers  for  the  ensuing  year 
were  installed  and  the  62nd  annual  meeting  of  the  American  Pharma- 
ceutical Association  was  declared  adjourned. 

Any  account  of  this  meeting  without  some  reference  to  the 
elaborately  planned  and  carefully  carried  out  social  features  would 
be  incomplete  at  best.  The  local  secretary  and  his  efficient  assistants 
had  for  the  nonce  devised  a  program  in  which  the  social  features  did 
not  conflict  with  the  business  meetings  of  the  Association  or  any  of 
its  sections,  and,  despite  the  very  liberal  duplication  of  section  ses- 
sions during  the  day,  the  evenings  were  free  to  all  but  Council  mem- 
bers and  delegates,  to  enjoy  as  they  saw  fit. 

The  program  as  arranged  served  not  alone  to  provide  large  and 
interested  audiences  at  all  of  the  sessions  of  the  Association,  but 
also  insured  ample  time  to  permit  members  of  the  Association  to 
take  part  in  the  several  outings  and  informal  gatherings  that  had 
been  provided. 

The  supper  and  smoker  on  Wednesday  evening  and  the  river 
excursion  on  Thursday  afternoon  were  attended  by  upwards  of  1000 
members  and  friends,  and  will  long  be  remembered  as  being  among 
the  most  unique  of  the  functions  heldi  in  connection  with  meetings  of 
the  American  Pharmaceutical  Association. 

The  graduates  of  the  Philadelphia  College  of  Pharmacy  present 
at  the  meeting  were  entertained  at  luncheon  on  Wednesday  at  noon 
by  Frank  G.  Ryan,  a  graduate  and  for  some  years  one  of  the  assistant 
professors  of  the  college.  A  total  of  53  graduates,  representing  21 
States,  was  present,  and  the  occasion  offered  an  unusual  opportunity 
to  make  and  to  renew  acquaintances  among  graduates  of  the  college. 

The  officers  of  the  American  Pharmaceutical  Association  for  the 
coming  year  are :  Honorary  president,  G.  H.  Schaefer,  Fort  Madi- 
son, Iowa ;  president,  Caswell  A.  Mayo,  New  York ;  vice-presidents, 
L.  D.  Havenhill,  Lawrence,  Kan.,  C.  H.  Packard,  Boston,  Mass., 
Chas.  Gietner,  St.  Louis,  Mo. ;  permanent  secretary,  W.  B.  Day, 


Am.  Jour.  Pharm. ) 
October,  1914.  J 


Identification  of  Artificial  Silks. 


471 


Chicago,  111. ;  treasurer,  H.  M.  Whelpley,  St  Louis,  Mo. ;  reporter  on 
the  progress  of  pharmacy,  C.  Lewis  Diehl,  Louisville,  Ky. 
The  nominees  to  be  voted  for  by  mail  are  : 

For  president :  W.  C.  Alpers,  Cleveland ;  W.  J.  Teeters,  Iowa 
City,  Iowa ;  L.  D.  Havenhill,  Lawrence,  Kan. 

For  first  vice-president :  C.  H.  LaWall,  Philadelphia ;  L.  A. 
Seltzer,  Detroit;  D.  F.  Jones,  Watertown,  S.  D. 

For  second  vice-president :  E.  H.  Ruddiman,  Nashville,  Tenn. ; 
E.  O.  Kagy,  Des  Moines,  Iowa ;  F.  W.  Nitardy,  Denver,  Col. 

For  third  vice-president:  L.  A.  Brown,  Lexington,  Ky. ;  E.  N. 
Gathercoal,  Chicago,  111.  ;  Cornelius  Osseward,  Seattle,  Wash. 

For  member  of  Council :  F.  M.  Apple,  Philadelphia  ;  Philip  Asher, 
New  Orleans;  E.  C.  Bent,  Dell  Rapids,  S.  D. ;  H.  V.  Amy,  New 
York ;  Charles  B.  Jordan,  Lafayette,  Ind. ;  R.  H.  Walker,  Gonzales, 
Tex. ;  J.  O.  Burge,  Nashville,  Tenn. ;  Andrew  Scherer,  Chicago ; 
Caswell  A.  Mayo,  New  York. 

The  191 5  meeting  of  the  Association  is  to  be  held  in  San 
Francisco,  Cal.,  at  a  time  to  b>e  fixed  by  the  Council. 


THE  IDENTIFICATION  OF  ARTIFICIAL  SILKS  ESPE- 
CIALLY PREPARED  FOR  THE  PRACTICAL  MILL 
MAN  AND  DYER/ 

By  Louis  J.  Matos,  Ph.D. 

Owing  to  the  constantly  increasing  use  of  artificial  silks  and  the 
consequent  confusion  arising  in  dye-houses  and  silk  mills  generally, 
due  to  the  occasional,  though  unintentional,  mixing  of  lots,  it  becomes 
a  matter  of  some  importance  for  the  dyer  or  manager  to  be  able  to 
identify  with  certainty  the  several  important  kinds  of  artificial  silks 
on  the  market. 

Where  a  dyer  goes  on  from  day  to  day  with  his  work,  and  on 
one  kind  of  silk,  it  is  a  matter  of  some  consequence  when  he  finds 
himself  confronted  with  the  problem  of  dyeing  a  new  lot  of  different 
kind  of  silk  that  does  not  come  out  as  expected,  or  which  seems  to 
offer  difficulties  during  the  dyeing. 

Many  instances  are  familiar  to  dyers  where  lots  of  mixed  artificial 
silk  have  been  sent  to  the  dye-house,  and  inequality  in  the  dyeing  was 

1  Reprinted  from  The  American  Silk  Journal;  Dyestuffs,  Dec.,  1913,  No.  12. 


472 


Identification  of  Artificial  Silks. 


{Am.  Jour.  Pharm. 
October,  1914. 


not  discovered  until  near  the  end  of  the  operation,  when  it  became 
a  matter  of  great  skill  to  bring  up  the  shade  of  the  indifferent  skeins 
to  the  shade  of  the  main  lot.  This  condition  could  have  been  antici- 
pated had  the  dyer  been  acquainted  with  the  fact  that  the  entire  lot 
of  silk  was  not  of  one  kind. 

From  time  to  time  there  have  been  published  tests  and  reactions 
with  chemicals  to  be  used  in  distinguishing  the  several  kinds  of  arti- 
ficial silks,  but  the  practical  application  of  which,  in  the  dye-house  or 
office,  seems  to  offer  some  obstacles  in  the  hands  of  those  not  actually 
acquainted  with  the  details  of  making  reactions.  It  seems  that  while 
the  method  of  making  the  tests  is  simple  enough,  the  greatest  difficulty 
is  in  having  the  solutions  or  reagents  properly  compounded  and  in 
conducting  the  tests  afterwards. 

Simple  descriptions  alone  do  not  seem  to  meet  the  case  entirely. 
Of  course,  there  is  nothing  to  take  the  place  of  a  practical  demon- 
stration of  a  testing  method  when  carried  out  by  one  who  is  practi- 
cally familiar  with  the  proper  sequence  of  the  operations. 

On  the  other  hand,  many  of  the  methods  for  fibre  testing  that 
have  been  published,  while  apparently  intended  for  dyers  and  prac- 
tical mill  men,  being  those  most  concerned,  are,  as  a  rule,  written 
for  the  chemist  with  some  experience,  as  only  such  could  possibly 
have  the  unusual  reagents  and  apparatus,  or  even  the  apparently  deli- 
cate manipulative  skill,  to  handle  both  satisfactorily. 

Without  question,  the  most  satisfactory  means  to  identify  artificial 
silk  is  to  make  use  of  the  microscope,  but  as  very  few  mills  are 
equipped  with  this  valuable  instrument,  and  fewer  still  are  proficient 
in  making  use  of  it,  we  will  omit  its  discussion  as  applied  to  artificial 
silk  and  confine  ourselves  exclusively  to  the  chemical  or  wet  methods 
that  experience  has  taught  us  as  being  the  most  satisfactory. 

To  identify  artificial  silk  properly  requires  that  the  person  at- 
tempting the  work  should  have  at  hand  a  small  set  of  chemical 
reagent  bottles  of  not  more  than  two-ounce  capacity  and  with  glass 
stoppers.  Such  bottles  are  not  costly  and  may  be  obtained  through  a 
local  druggist ;  the  style  known  as  "  XX  Tinctures  "  are  admirably 
suited  for  the  purpose.  They  are  to  be  filled  with  the  following 
reagents,  which  can  be  procured  from  a  chemical  supply  house  or  pre- 
pared by  a  friendly  pharmacist  or  chemical  friend. 

The  following  constitutes  the  list  and  the  methods  for  their 
preparation : 


Am6cSerj9hi4rm'}       Identification  of  Artificial  Silks.  473 

No.  I.    Glycerinated  Sulphuric  Acid. 

Pure  Glycerin    10  c.c. 

Distilled  Water   5  c.c. 

Add  slowly  with  constant  stirring,  a  few  drops  at 

a  time,  Pure  Concentrated  Sulphuric  Acid   15  c.c. 

No.  2.   Iodo-iodide  of  Potassium. 

Distilled  Water   30  c.c. 

Potassium  Iodide    0.3  gr. 

Iodine,  an  excess. 
No.  3.    Chlor-iodide  of  Zinc. 

Distilled  Water   30  c.c. 

Fused  Chloride  of  Zinc  .  ..  1.75  gr. 

Filter  and  add  to  clear  nitrate  Iodine  to  saturation. 
No.  4.    Cold  Concentrated  Sulphuric  Acid. 
No.  5.  Half  Saturated  Chromic  Acid. 
No.  6.  A  40  per  cent.  Caustic  Potash  Solution. 
No.  7.  Copper-Oxide-Ammonia. 

This  is  an  important  reagent  in  all  fibre  work.   It  should  be  made 
with  great  care  by  preparing  a  solution  of  copper  oxide  in  ammonia  to 
saturation,  and  passing  through  it  a  current  of  air  freed  from  carbon 
dioxide,  by  first  being  passed  through  a  solution  of  caustic  potash. 
No.  8.    Nickel  Oxide  Ammonia. 

Nickel  Sulphate  in  crystals   2  gr. 

Water   30  c.c. 

Precipitate  the  nickel  with  caustic  soda  and  filter;  then  dissolve 
the  precipitate  in  a  mixture  of : 

Concentrated  Ammonia    8  c.c. 

Water    8  c.c. 

No.  9.    Alkaline  Copper  Glycerin  Solution. 

Sulphate  of  Copper   3  gr. 

Water    30  c.c. 

Glycerin    1 .75  gr. 

to  which  is  added  a  sufficient  quantity  of  caustic  potash  solution  to 
precipitate  the  copper  and  redissolve  it. 

No.  10.    Diphenylamine-Sulphuric  Acid  Solution. 

Diphenylamine   1.57  gr. 

Concentrated  Sulphuric  Acid    25  c.c. 

The  operator  should  keep  these  bottles  in  a  closet  when  not  in 
use  and  at  all  times  free  from  dust.  The  label,  besides  the  name, 
should  also  have  the  formula  written  upon  it. 


474  Identification  of  Artificial  Silks.       \  A™koZri9um' 

The  apparatus  required  to  make  the  tests  consists  of  a  dozen 
small  plain  white  butter  dishes,  a  dozen  small  test-tubes  of  short 
length  and  not  over  half  an  inch  in  diameter,  and  a  spirit  lamp  or 
Bunsen  burner  to  supply  heat.  There  should  also  be  at  hand  two 
small  bottles  or  tubes  containing  red  and  blue  litmus  paper.  The 
entire  outfit  is  procurable  under  five  dollars. 

There  are  five  kinds  of  artificial  silk  generally  met  with  in  com- 
merce, as  follows: 

Collodium  Silk  (Strictly  nitro  silks). 

Cellulose  Silks. 

Viscose  Silks. 

Acetate  Silks.  '  • 

Gelatin  Silks. 

The  first  important  test  to  make  is  to  determine  whether  the  silk 
under  examination  is  made  from  gelatin  or  not. 

Take  one  of  the  test-tubes,  see  that  it  is  clean  and  dry  inside,  and 
place  at  the  bottom  of  it  a  small  tuft  of  the  silk  about  the  size  of  a 
small  pea  when  rolled  between  the  fingers.  In  the  open  end  of  the 
tube  insert  a  piece  of  red  litmus  paper,  bending  the  end  over  so  that 
the  strip  will  not  slide  down  the  tube. 

With  a  handle  made  of  several  folds  of  paper  around  the  neck 
of  the  tube  so  as  to  permit  one  to  hold  it  comfortably,  place  the  closed 
end  of  the  tube  in  the  flame  of  the  Bunsen  burner  or  spirit  lamp, 
giving  the  tube  a  slight  to  and  fro  motion  until  the  fibres  in  the  tube 
begin  to  char  and  vapors  are  seen  to  arise.  When  these  vapors  are 
observed  to  come  out  of  the  open  end  of  the  test-tube,  note  whether 
the  color  of  the  red  litmus  paper  changes  to  blue.  If  such  a  change 
takes  place  it  is  due  to  the  presence  of  ammonia  gas  resulting  from 
the  charring  of  the  fibres  and  which  could  only  come  from  gelatin 
silk.  These  vapors  may  also  have  the  odor  of  burning  horn  or  hair, 
which  odor  is  further  indicative  of  the  presence  of  gelatin. 

On  the  other  hand,  if  the  litmus  paper  does  not  change  color, 
acid  fumes  may  be  present  and  are  to  be  confirmed  by  repeating 
the  test,  but  using  blue  litmus  paper,  and  upon  it  turning  red, 
indicates  that  the  silk  may  be  any  one  of  the  four  above-named 
makes. 

To  distinguish  finally  between  the  several  artificial  silks  emitting 
acid  fumes  with  heat,  place  two  of  the  butter  dishes  side  by  side ; 
in  one,  place  some  of  the  silk  fibre  and  upon  it  pour  some  of  reagent 
No.  i,  and  let  soak  for  a  few  minutes,  and  then  afterwards  add  a 


A^'ctJoror;r9hitm'}       Identification  of  Artificial  Silks.  475 

few  drops  of  reagent  No.  2.  In  the  second  dish  put  some  of  the 
fibre  and  a  small  amount  of  reagent  No.  3,  and  note  carefully  what 
changes  in  color,  if  any,  take  place.  If  both  samples  show  a  dis- 
tinct yellow  coloration,  the  silk  is  Acetate  Silk. 

On  the  other  hand,  if  the  coloration  is  blue,  the  silk  may  be 
either  collodium,  cellulose  or  viscose  silk,  which  is  confirmed  if  the 
coloration  shown  in  the  second  dish  is  reddish-violet.  To  differen- 
tiate between  these  three  silks  just  mentioned,  place  a  small  tuft  of 
the  fibres  in  a  dry  dish  and  pour  upon  it  a  small  amount  of  cold 
concentrated  sulphuric  acid  (No.  4).  If  the  silk  dissolves  rapidly, 
the  specimen  is  either  collodium  or  viscose  silk ;  cellulose  silk,  i.e., 
Pauly,  Fremery,  etc.,  dissolves  slowly. 

Confirmatory  tests  are  made  in  test-tubes  with  the  chromic  acid 
solution  (No.  5)  in  the  cold,  when  these  three  silks  dissolve  grad- 
ually, and  upon  the  tube  being  heated,  dissolve  quickly.  When 
treated  in  the  same  manner  with  warm  caustic  potash  solution 
(No.  6)  these  three  silks,  together  with  the  acetate  silk  show  a  dis- 
tinct swelling,  while  gelatin  silk  dissolves  rapidly  and  completely. 

The  copper  oxide  ammonia  test  (No.  7)  when  applied  in  a  test- 
tube  first  causes  a  swelling  and  dissolves  collodium  and  viscose  silks, 
but  acetate  silk  swells  without  dissolving,  and  gelatin  silk  takes 
a  bluish-violet  coloration  without  dissolving. 

The  nickel-oxide-ammonia  reagent  (No.  8),  when  applied  both 
cold  and  warm  to  a  sample  of  artificial  silk  in  the  test-tube,  causes 
a  swelling  of  the  fibres  but  without  dissolving  them.  This  applies 
to  collodium,  cellulose,  viscose,  and  acetate  silk,  but  not  to  gelatin 
silk,  which  latter  takes  a  brown  coloration  without  dissolving. 

The  alkaline-copper-glycerin  solution  (No.  9)  has  no  action  even 
after  long  boiling  upon  the  first  four  silks  above  mentioned,  but 
gelatin  silk  dissolves  after  a  short  time. 

A  convenient  reagent  for  artificial  silk  is  the  concentrated 
sulphuric  acid-diphenylamine  solution  (No.  10)  which  has  been 
extolled  as  the  one  reagent  for  this  class  of  work,  but  as  a  matter 
of  fact  its  usefulness  is  limited  exclusively  to  differentiate  only  the 
nitro  silks  from  the  others.  With  nitro  silks  of  the  Chardonnet 
type,  it  causes  a  distinct  blue  coloration,  while  the  other  silks 
remain  uncolored.  This  diphenylamine  reaction  lasts  but  a  com- 
paratively short  time,  reaching  its  maximum  intensity  within  five 
minutes  after  adding  the  reagent,  when  it  gradually  disappears. 

In  order  to  be  in  the  position  where  one  can  absolutely  and 


476 


Book  Reviews. 


J  Am.  Jour.  Pharm. 
t     October,  1914. 


certainly  pass  judgment  upon  the  identity  of  a  given  silk  sample, 
the  operator  should  have  at  hand  a  collection  of  true  type  samples 
obtained  directly  from  the  artificial  silk  manufacturers  and  to  make 
the  above  outlined  reactions  repeatedly,  systematically  and  with 
care.  By  care  is  meant  not  being  too  hasty  in  forming  a  con- 
clusion, and  to  disregard  and  reject  completely  any  test  that  one 
may  have  made,  into  which  the  element  of  doubt  enters. 

With  such  a  set  of  proved  samples  at  hand  and  a  set  of  reagents 
as  above  outlined,  when  unusual  lots  are  received  by  the  dye-house, 
or  where  silk  is  received  from  unfamiliar  sources,  its  identity  can 
be  accurately  determined. 

The  foregoing  details  refer  to  undyed  artificial  silk,  but  to  identify 
dyed  silk  by  chemical  means  requires  that  it  should  be  stripped 
of  its  color,  which  is  generally  very  easily  accomplished  by  means  of 
Hyraldite  or  some  other  equally  efficient  stripping  agent. 


BOOK  REVIEWS. 

The  Art  of  Compounding.  A  Text-Book  for  Students  and  A 
Reference  Book  for  Pharmacists  at  the  Prescription  Counter.  By 
Wilbur  L.  Scoville,  Ph.  G.,  formerly  Professor  of  Theory  and  Prac- 
tice of  Pharmacy  in  the  Massachusetts  College  of  Pharmacy ;  member 
of  the  Eighth  Committee  on  Revision  of  the  United  States  Pharma- 
copoeia and  of  the  Second  and  Third  Committees  of  the  Revision  of 
the  National  Fomulary.  Fourth  edition,  revised  and  enlarged,  with 
76  illustrations.  Philadelphia :  P.  Blakiston's  Son  &  Co.,  1012  Walnut 
Street.   $3  net. 

This  excellent  volume,  prepared  by  the  author  when  he  was  a 
professor  in  the  Massachusetts  College  of  Pharmacy,  has  become  one 
of  the  most  popular  books  on  the  prescription  and  its  compounding 
that  we  have.  That  it  has  run  through  four  editions  shows  that  both 
the  publisher  and  author  are  alive  to  the  progress  that  is  being  made 
in  pharmacy  and  the  development  of  this  subject  in  particular. 
Among  the  innovations  in  the  present  volume  may  be  mentioned  the 
inclusion  of  illustrations.  These  are  numerous,  and  not  only  include 
the  implements  for  preparing  small  quantities  of  remedies-,  as  in 
general  prescription  work,  but  also  the  forms  and  apparatus  in  use  by 
manufacturers.    The  author's  wide  experience  in  all  phases  of  the 


Am.  Jour.  Pharm.  1 
October,  1914.  J 


Book  Reviews. 


477 


drug  business  makes  him  unusually  well  qualified  to  handle  manu- 
facturing processes  in  a  practical  way. 

For  the  purpose  of  adding  interest  to  the  study  of  individual 
prescriptions,  some  225  prescriptions  from  State  Board  examinations 
have  been  added  in  a  systematic  way.  This  compilation  will  be 
found  to  be  of  great  value  to  the  apprentice  in  his  study  of  the  methods 
of  mixing  and  conditions  suitable  for  their  compounding.  A  valuable 
chapter  on  biological  products  has  been  added  and  will  prove  of  great 
interest  to  pharmacists.  The  new  developments  in  the  pharmaceutical 
applications  of  sterilization  are  noted  in  several  portions  of  the  book. 

The  Electrical  Conductivity  and  Ionization  Constants  of 
Organic  Compounds.  A  bibliography  of  the  periodical  literature 
from  1889  to  19 10  inclusive,  including  all  important  work  before  1889 
and  corrected  to  the  beginning  of  19 13.  Giving  numerical  data  for 
the  ionization  constants  at  all  temperatures  at  which  they  have  been 
measured ;  and  some  numerical  data  of  the  electrical  conductivity. 
By  Heyward  Scudder.  New  York :  D.  Van  Nostrand  Company,  25 
Park  Place.    1914.   $3  net.  1 

This  is  a  very  valuable  compilation,  containing  all  of  the  valuable 
data  on  the  electrical  conductivity  and  ionization  of  organic  com- 
pounds, practically  everything  of  value  being  included,  with  very  few 
exceptions.  The  references  to  subjects  of  biological  interest,  as 
albumin,  blood,  sap,  etc.,  are  complete  only  for  the  last  few  years 
(roughly,  the  last  five  or  ten),  but  afford  a  means  both  of  knowing 
where  to  get  at  the  important  work,  which  is  all  recent,  and  where  to 
start  in  any  more  thorough  search  of  the  literature.  Neither  are  the 
references  to  the  resistance  of  substances  such  as  rubber,  wood,  etc., 
given,  as  they  are  of  value  chiefly  in  connection  with  the  question  of 
electrical  insulation,  although  they  have  some  biological  interest. 
References  to  the  conductivity  of  inorganic  compounds  in  organic 
solvents  have  not  been  looked  up  specially,  though  in  cases  where  salt 
formation  is  to  be  expected  they  have  been  taken.  In  addition,  a 
number  of  references  are  given  on  the  conductivity  of  molten  salts 
as  well  as  certain  inorganic  compounds.  In  the  tables  a  number  of 
references  are  given  to  the  work  on  the  comparative  strength  of 
different  compounds  (measured  in  various  ways),  because  to  many 
chemists  the  chief  value  of  the  ionization  constant  of  a  compound, 
or  of  a  measurement  of  its  electrical  conductivity,  is  to  determine  its 
strength  as  an  acid  or  a  base. 


478 


Book  Reviews. 


<  Am.  Jour.  Pharm. 
t     October,  1914. 


The  book  is  divided  into  a  set  of  tables  arranged  according  to 
the  names  of  the  compounds,  containing  all  the  data  that  may  be 
given,  with  a  bibliography  of  all  the  references  to  each  compound ; 
a  formula  index  to  the  compounds  ;  a  bibliography  arranged  according 
to  the  names  of  authors;  a  subject  index  to  certain  subjects;  and  a 
journal  list  giving  the  names  of  all  journals  examined,  with  the 
number  and  date  of  the  last  volume  examined. 

Chemical  Reagents.  Their  Purity  and  Tests.  Authorized 
translation  of  "  Priifung  der  Chemischen  Reagenzien  auf  Reinheit  " 
(Zweite  Auflage)  von  E.  Merck.  By  Henry  Schenck,  Second  edition. 
New  York:  D.  Van  Nostrand  Company,  25  Park  Place.  1914.  $1 
net. 

This  translation  in  method  of  treatment,  closely  resembles  that  of 
the  German  work.  It  includes,  however,  numerous  articles  which 
have  come  into  prominence  since  the  earlier  work  was  published. 
Among  the  subjects  included  for  the  first  time  in  this  edition  the 
following  may  be  mentioned :  Alphanaphthylamine,  Ammonium 
Chromate,  Ammonium  Molybdate  Solution,  Ammonium  Persulphate, 
Benzidine  for  Blood  Test,  Bismuth  and  Potassium  Iodide  Solution, 
Carbon  Tetrachloride,  Carmin-Fibrin,  Chromium  Trioxide  for 
Carbon  Determination,  Cobalt  Nitrate  (Free  from  Nickel),  Cobalt 
Oxide,  Copper  Hydroxide,  Copper  Oxide-Asbestos,  Devarda's  Metal, 
Dicyandiamidine  Sulphate,  Dimethylglyoxime,  Dimethylparaphenyl- 
enediamine  Hydrochloride,  Ferric  Oxide,  Glass  Wool,  Hydrazine 
Sulphate,  Indigo  Carmin,  Indigo  Solutions,  Lead  Peroxide,  Granu- 
lated Magnesia  Mixture,  Magnesite,  Manganese  Metaphosphate  Solu- 
tion, Methyl  Red,  Platinized  Pumice  Stone,  Poirrier's  Blue  C4B, 
Potassiijm  Persulphate,  Quartz  Sand,  Sea  Sand,  Silver-Asbestos, 
Sodium-Cobaltic  Nitrate  Solution,  Tetramethylparaphenylenedia- 
mine  Hydrochloride,  Yellow  Oxide  of  Mercury. 

A  number  of  changes  have  been  made,  some  of  these  having 
materially  raised  the  standard  of  purity.  Coincident  with  this  im- 
provement is  the  inclusion  among  the  references  of  important  new 
contributions  upon  the  uses  and  methods  of  testing  reagent  chemicals. 
The  tables  of  equivalents  of  standard  solutions  have  been  replaced, 
in  response  to  a  suggestion,  by  a  table  giving  approximate  strengths 
and  brief  directions  for  the  preparation  of  solutions  for  reagent  pur- 
poses, compiled  from  published  writings.  Another  valuable  feature 
in  this  translation  is  the  parenthetical  statement  appended  to  each 


Am.  Jour.  Pharm.  ) 
October,  1914.  j 


Book  Reviews. 


479 


test,  giving  in  terms  of  percentage  the  minimum  amount  of  the 
impurity  which  would  be  recognized  by  the  test.  This  work  will  be 
found  of  very  great  value  to  analysts  in  the  examination  of  reagents. 

A  Critical  Revision  of  the  Genus  Eucalyptus.  By  J.  H. 
Maiden,  Government  Botanist  of  New  South  Wales  and  Director  of 
the  Botanic  Gardens,  Sydney.  Parts  XVIII  to  XXI.  Published  by 
authority  of  the  Government  of  the  State  of  New  South  Wales. 
Sydney:  William  Applegate  Gullick,  Government  Printer.  1913. 

These  valuable  monographs  by  Mr.  Maiden  continue  to  be  of  very 
great  interest.  In  the  most  recent  pamphlets  the  following  species 
are  critically  considered :  Eucalyptus  macrocarpa,  Hook,  Eucalyptus 
Preissiana,  Schauer,  Eucalyptus  megacarpa,  F.  v.  M.,  Eucalyptus 
globulus,  Labillardiere,  Eucalyptus  Maideni,  F.  v.  M.,  Eucalyptus 
umigera,  Hook  f .,  Eucalyptus  goniocalyx,  F.  v.  M.,  Eucalyptus  nitens, 
n.  s.  d.,  Eucalyptus  elceophora,  F.  v.  M.,  Eucalyptus  cordata,  Labill., 
Eucalyptus  angustissima,  F.  v.  M.,  Eucalyptus  gigantea,  Hook,  Eu- 
calyptus longifolia,  Link  and  Otto,  Eucalyptus  diversicolor,  F.  v.  M., 
Eucalyptus  Guilfoylei,  Maiden,  Eucalyptus  patens,  Bentham,  Eu- 
calyptus Todtiana,  F.  v.  M.,  Eucalyptus  micranthera,  F.  v.  M.,  Eu- 
calyptus cinera,  F.  v.  M.,  Eucalyptus  pulverulenta,  Sims,  Eucalyptus 
cosmophylla,  F.  v.  M.,  Eucalyptus  gomphocephala,  A.  P.  DC. 

Annales  du  Musee  Colonial  de  Marseille  fondees  en  1893  par 
M.  Le  Professeur  Dr.  Edouard  Heckel  et  publies  sous  sa  direction. 
Vingt-et-unieme  anne,  3e  series  ier  volume  (1913).  Marseille  Musee 
colonial  5,  Rue  Noailles,  5  1913. 

This  volume  contains  the  following  monographs  :  Palms  of  Mada- 
gascar, by  MM.  H.  Jumelle  and  H.  Perrier;  Botanical  Study  of  Cay- 
sen,  aii  Oleaginous  Seed  of  Sapotacese,  by  Narcel  Dubard ;  Contribu- 
tions to  the  Anatomy  of  the  Dypsidese  Palms  of  Madagascar,  by  M.  J. 
Achilli;  The  Orchidaceae  of  Madagascar,  by  M.  R.  Schlechter;  The 
Cultivated  Plants  of  Central  Africa,  by  M.  A.  Baudon ;  A  Melastoma- 
ceous  Plant  Osbeckiees  malgaches,  by  PL  Jumelle  and  H.  Perrier ; 
Analysis  of  a  Tabachir  of  Indo-China,  by  E.  Laborde. 

A  large  number  of  very  excellent  drawings  and  photographs  ac- 
company this  volume,  and  the  researches  are  of  very  high  class.  The 
first  volume  of  the  Colonial  Museum  of  Marseilles  was  published  in 
1893,  so  that  for  more  than  twenty' years  the  studies  on  products  of 
the  French  colonies  have  been  published,  reflecting  very  great  credit 
upon  the  director,  Professor  Heckel. 


480 


Obituaries. 


(Am.  Jour.  Pharm. 
1    October,  1914. 


OBITUARIES. 
David  H.  Ross. 

David  H.  Ross,  of  the  class  of  '78,  died  at  his  residence  and  place 
of  business,  Almond  and  Norris  Streets,  Philadelphia,  after  a  brief 
illness  due  to  pneumonia.  At  the  time  of  his  death  he  was  69  years  of 
age  and  had  conducted  a  retail  drug  business  at  his  home  address  for 
nearly  thirty  years.  Mr.  Ross  was  born  in  Ireland  of  Scotch  parent- 
age, and  came  to  Philadelphia  in  his  youth.  His  experience  in  the 
drug  business  was  acquired  with  the  firm  of  Bullock  and  Crenshaw, 
for  whom  he  worked  as  a  drug  clerk,  and,  after  his  graduation,  as  a 
salesman.  Nearly  all  his  life  the  deceased  was  active  in  pharma- 
ceutical affairs,  and  held  many  positions  of  honor  and  trust. 

He  was  president  of  the  Alumni  P.  C.  P.  in  1893;  and  for  many 
years  was  secretary-treasurer  of  the  Philadelphia  Wholesale  Drug 
Company.  The  Philadelphia  Association  of  Retail  Druggists,  of 
which  he  was  an  active  member,  also  made  use  of  the  services  of 
Mr.  Ross  on  many  occasions.  He  was  also  made  treasurer  of  the 
Druggists'  Building  and  Loan  Association  when  it  was  organized  a 
short  time  ago.  He  was  active  in  the  management  of  the  First 
Presbyterian  Church  of  Kensington,  of  which  he  was  an  elder.  In 
addition  to  his  other  activities,  he  for  many  years  took  a  practical  in- 
terest in  political  matters  and  served  on  the  Executive  Committee  of 
the  Washington  party,  and  was  elected  to  Councils  upon  the  Reform 
party  ticket.  He  also  served  as  a  school  director  in  his  home  ward 
for  a  number  of  years. 

Personally  Mr.  Ross  was  aggressive  and  active  in  everything  he 
took  in  hand,  and  was  unusually  outspoken  and  frank  in  attacking 
what  he  considered  wrong;  and  was  just  as  quick  to  defend  what  he 
considered  to  be  right,  in  the  same  characteristic  manner.  Behind  the 
aggressive  man  of  action  there  was,  however,  a  true  man  in  the 
broader  human  sense  who  endeared  himself  by  strong  ties  to  those 
who  learned  to  know  him  well. 

W.  L.  Cliffe. 

Peter  P.  Fox. 

Peter  P.  Fox,  of  the  class  of  1858  of  the  Philadelphia  College  of 
Pharmacy,  died  on  April  24,  19 14.  He  was  one  of  the  oldest  gradu- 
ates of  the  College,  and  had  been  a  member  since  1872.  Mr.  Fox  was 
born  in  Leimbach,  near  Audenaw,  Germany,  in  1835.  He  was  a 
Brother  of  Prof.  John  Fox,  M.D.,  who  graduated  from  the  University 


Am.  Jour.  Pharm.  ) 
October,  19  L4.  j 


Current  Literature. 


481 


of  Bonn,  Germany,  and  was  prominently  known  before  the  Civil  War 
as  a  teacher  of  languages  to  the  children  of  many  of  our  conspicuous 
families  of  those  days  in  Philadelphia.  In, the  War  of  the  Rebellion 
he  enlisted  in  the  99th  Pennsylvania  Volunteer  Infantry,  and  served 
for  two  years  and  eight  months.  At  the  expiration  of  his  service  he 
came  to  Philadelphia  and  started  a  drug  store  at  Seventy-third  Street 
and  Woodland  Avenue,  West  Philadelphia,  where  he  continued  the 
business  until  his  death.  Mr.  Fox  was  allied  with  the  American 
Pharmaceutical  Association,  the  Philadelphia  Association  of  Retail 
Druggists,  and  various  other  bodies.  The  funeral  of  Mr.  Fox  took 
place  on  Monday,  April  27th,  with  a  Solemn  Requiem  Mass  at  St. 
Clement's  Church,  Paschalville,  of  which  he  was  a  devout  com- 
municant for  many  years.  The  remains  were  laid  at  rest  in  New 
Cathedral  Cemetery. 


CURRENT  LITERATURE. 
Gaseous  Impurities  in  the  Air  of  Railway  Tunnels. — 
Seidell  and  Meserve,  in  Hygienic  Laboratory  Bulletin  No.  92,  have 
taken  up  the  question  of  the  composition  of  the  air  in  railway 
tunnels,  and  summarize  their  work  as  follows : 

(a)  On  account  of  the  particular  conditions  in  hand,  methods  for 
the  determination  of  sulphur  dioxide  based  upon  the  aspiration  of  the 
sample  through  a  small  volume  of  liquid  followed  by  a  gravimetric  or 
volumetric  determination  of  the  retained  sulphur  dioxide  could  not 
be  used.  The  several  possible  variations  of  the  iodometric  titration 
were  examined  and  the  general  source  of  the  errors  discussed.  It 
was  finally  shown  that  a  method  of  direct  titration  with  N/1000 
iodine  solution  gave,  after  applying  proper  correction  factors,  results 
of  satisfactory  accuracy. 

(b)  Experiments  upon  the  rate  of  loss  of  sulphur  dioxide  on 
standing  showed  that  in  the  presence  of  moisture  only  a  small  fraction 
of  the  used  sulphur  dioxide  was  recovered  after  one  hour.  In  dry 
bottles  there  is  usually  an  inconsiderable  loss  within  the  first  two 
hours,  although  with  very  dilute  mixtures  an  appreciable  loss  may 
occur  after  one-fourth  to  one-half  hour. 

(c)  Of  quite  small  amounts  of  sulphur  dioxide  liberated  in  a 
closed  room  only  about  30  to  60  per  cent,  could  be  recovered,  depend- 
ing upon  the  amount  of  stirring  and  the  moisture  content  of  the  air. 

(d)  In  adapting  the  iodine  pentoxide  method  to  the  determina- 
tion of  carbon  monoxide  in  the  samples  of  tunnel  air,  manipulative 
improvements  involving  the  use  of  a  new  form  of  absorption  bulb  and 


482 


Current  Literature. 


{Am.  Jour.  Pharm. 
October,  1914. 


of  a  closed  aspiration  system  were  developed.  The  time  for  a  deter- 
mination was  decreased  to  about  one-fourth  and  the  attention  which 
the  apparatus  required  during  the  passage  of  the  sample  through  it 
was  reduced  to  a  minimum. 

(e)  Analyses  of  mixtures  of  very  small  amounts  of  carbon  mon- 
oxide with  air  showed  that  from  88  to  98  per  cent,  of  the  amount 
present  was  recovered  by  the  method.  On  account  of  the  very  small 
actual  amounts  under  consideration,  these  losses  are  considered 
negligible.  ,  , 

(/)  The  results  of  the  analyses  of  88  samples  of  air  from  the  two 
tunnels  show  that  on  an  average  there  is  approximately  five  times  as 
much  of  each  of  the  two  gases  in  the  Fulton  as  in  the  electrified 
tunnel.  In  the  case  of  the  Fulton  Tunnel,  the  highest  amounts  were 
15.1  parts  of  sulphur  dioxide  per  million  and  267  parts  of  carbon 
monoxide  per  million.  The  corresponding  figures  for  the  electrified 
tunnel  were,  respectively,  2.9  parts  and  25  parts. 

(g)  A  review  of  the  available  literature  upon  the  physiological 
effects  of  small  amounts  of  carbon  monoxide  and  sulphur  dioxide 
showed  that  the  concentrations  of  these  gases  which  produced  an 
unmistakable  harmful  effect  upon  man  were  somewhat  greater  than 
the  maximum  amounts  which  were  found  in  any  of  the  tunnel-air 
samples. 

Kieselguhr  Industry. — P.  A.  Borck  in  an  article  {Met all.  and  ' 
Client.  Engin.,  xii,  109). — This  article  treats  of  the  properties  of 
kieselguhr,  its  occurrence  at  Lompoc,  California,  and  other  places, 
and  its  treatment.  Natural  blocks  can  be  obtained  by  sawing  the 
material ;  these  blocks  are  fairly  strong,  have  high  insulating  value, 
stand  heat  and  cold  well,  except  as  to  a  slight  shrinkage,  and  melt  at 
16100  C.  Light-weight  kieselguhr  bricks  are  produced  by  properly 
burning  the  material ;  they  insulate  well  up  to  red-heat,  but  shrink  at 
high  temperatures,  and  must  be  protected  against  sudden  changes 
of  temperature.  They  are  recommended  as  backing  for  more  refrac- 
tory bricks. — Jour.  Franklin  Ins.,  1914,  p.  382. 

Supply  of  Pollantin  Affected  by  War. — Fritzsche  Brothers, 
New  York,  advise  that  their  stock  of  Pollantin  Liquid  (Dunbar's 
serum  in  hay  fever)  is  exhausted ;  and  that,  due  to  the  lamentable  war 
conditions,  they  are  unable  to  replenish  in  time  for  the  current  sea- 
son's demand. 

Also,  that  but  a  very  limited  supply  of  the  Pollantin  Powder  and 
Ointment  is  available. 


THE  AMERICAN 


JOURNAL  OF  PHARMACY 


By  A.  F.  Sievers,  Chemical  Biologist,  Office  of  Drug-Plant  and  Poisonous- 
Plant  Investigations,  Bureau  of  Plant  Industry,  U.  S.  Department 
of  Agriculture. 

Since  commercial  cultivation  of  belladonna  has  become  a  ques- 
tion of  practical  possibility,  the  methods  of  cultivation  are  receiving 
more  and  more  attention.  Repeated  attempts  at  field  sowing  have 
demonstrated  quite  thoroughly  that  such  methods  are  not  successful. 
The  tenderness  and  slow  growth  of  the  young  plants  make  it  a 
difficult  matter  to  secure  a  proper  stand  by  that  method,  even  if  the 
seed  germinate  well  and  seasonal  conditions  are  favorable.  Loss  by 
insects  and  suffocation  by  weeds  are  the  principal  obstacles  encoun- 
tered after  the  plants  have  made  their  appearance.  One  of  the  main 
difficulties,  however,  lies  in  the  fact  that  belladonna  seed  germinates 
very  slowly  and  irregularly,  and,  as  a  rule,  not  much  over  50  per  cent, 
germinates  at  all. 

During  the  course  of  several  years  many  belladonna  plants  have 
been  propagated  by  the  writer  in  the  greenhouses  with  very  good 
success.  With  proper  care  and  the  elimination  of  such  disturbing 
factors  as  have  already  been  mentioned,  the  plants  grow  rapidly  and 
uniformly.  It  was  these  experiments  that  afforded  an  opportunity 
of  studying  carefully  the  behavior  of  belladonna  seed  and  its  relative 
vitality.  Lack  of  uniformity  in  germination  and  the  relatively  large 
percentage  of  inert  seed  were  noted  .repeatedly.  It  was  decided, 
therefore,  to  undertake  some  systematic  examination  of  the  seed 
with  a  view  to  establishing  what  types  of  seed  as  regards  size, 
weight,  and  color,  and  what  methods  of  handling  are  the  most 
desirable. 


THE  GERMINATION  OF  BELLADO 


NOVEMBER,  1914. 


*  Published  by  permission  of  the  Secretary  of  Agriculture. 

(483) 


484 


The  Germination  of  Belladonna  Seed. 


Am.  Jour.  Pharm. 
[  November,  1914. 


Methods  of  Study. 
In  the  experiments  which  were  conducted  in  the  greenhouse, 
the  seeds  were  planted  in  pots  of  convenient  size  containing  good 
loose  soil.  The  surface  was  marked  off  in  rows  about  three-quarters 
of  an  inch  apart,  and  the  same  number  of  seeds  were  placed  in  each 
pot  for  each  experiment.  The  seeds  were  planted  about  a  quarter  of 
an  inch  deep,  and  a  thin  layer  of  sand  was  scattered  over  the  surface. 
Suitable  conditions  of  moisture  and  temperature  were  constantly 
maintained. 

Effects  of  Freezing  on  the  Germination. 
Experience  has  shown  that  seed  sown  late  in  fall  usually  ger- 
minates quickly  in  spring,  while  spring-sown  seed  is  much  slower  in 
germinating.  This  fact  pointed  to  the  possibility  that  frost  might 
have  a  favorable  effect  in  hastening  germination.  As  a  definite  test 
a  small  lot  of  seed  was  divided  into  two  parts,  one  to  serve  as  a 
check  and  the  other  half  to  be  frozen.  The  freezing  was  accom- 
plished by  placing  the  seeds  in  a  test-tube  with  sufficient  water  to 
cause  them  to  cling  together,  and  then  subjecting  the  tube  to  a  tem- 
perature of  — 12°  C.  for  five  hours.  Forty-eight  seeds  from  this 
frozen  lot  were  sown  in  one  side  of  a  io-inch  pot,  while  the  same 
number  of  seeds  from  the  untreated  lot  were  sown  in  the  other  half 
as  a  check.  These  seeds  were  sown  on  April  13th.  The  following 
table  gives  the  number  and  per  cent,  germinated  at  various  intervals : 

Table  I. 

Germination  of  Frozen  and  Unfrozen  Seeds  Sown  on  April  ijth. 


Germination 

Description 

Number 

Per  cent. 

May 

,  May 

May 

May 

May 

May 

May 

May 

8 

IS 

22 

29 

8 

IS 

22 

29 

Frozen  

22 

24 

25 

26 

46 

50 

52 

54-2 

Check  (unfrozen) 

5 

IO 

12 

13 

IO.4 

20.8 

27 

29,2 

Figure  1  shows  graphically  the  percentage  of  total  germination 
at  each  observation.  The  effect  of  freezing  is  immediately  apparent, 
and  the  possibility  suggests  itself  of  hastening  the  germination  of 
the  seeds  in  greenhouse  work  by  subjecting  them  either  to  cold 
weather  or  some  such  treatment  as  described  above.    It  also  empha- 


Am.  Jour.  Pharm 
November,  1914 


nJ   The  Germination  of  Belladonna  Seed. 


485 


sizes  the  value  of  fall  sowing  in  case  direct  field  sowing  is  resorted 
to.  It  is  probable  that  the  influence  of  the  low  temperature  is  largely 
to  accelerate  germination  rather  than  to  induce  seeds  to  germinate 


Fig.  1. — Percentage  of  germination  of  frozen  and  unfrozen  seed  sown  on  April  13th. 


which  would  not  otherwise  do  so.  If  this  experiment  had  been 
carried  sufficiently  far  it  would  very  likely  have  been  found  that  the 
check  lot  would  eventually  show  a  percentage  of  germination  not 
much  less  than  that  of  the  frozen  lot. 


486 


The  Germination  of  Belladonna  Seed,   j  ^oveX/wiT' 


Relation  of  Size  of  the  Seed  to  Its  Germination. 
Considerable  variation  in  size  exists  among  belladonna  seed.  The 
average  seed  is  about  one  and  a  quarter  millimetre  in  diameter, 
while  the  extremes  range  from  less  than  one  to  almost  two  millimetres. 
In  order  to  determine  the  relative  weight  of  these  small  and  large 
seeds,  500  of  both  the  largest  and  smallest  seeds  were  separated  and 
weighed  in  portions  of  100  each.    Table  II  shows  the  results. 

Table  II. 

Relative  Weight  of  Large  and  Small  Seeds. 


Description 

Weight  (Gms.) 

Large 

Small 

First  100  

O.I29O 
O.I276 
O.I324 

0.1350 
O.I382 

O.0897 
O.082O 
O.0847 
O.0825 
O.0906 

Second  100  

Third  100  

Fourth  100 
Fifth  100  

Total  

Average  for  100. 

0.6622 
O.I324 

O.4295 
O.0859 

To  determine  the  relative  germination  of  these  seeds,  300  of  each 
were  sown  in  two  rectangular  boxes  on  April  5th.  Each  box  was 
divided  into  20  rows,  with  15  seeds  in  each  row.  Figure  2  shows 
graphically  the  resulting  germination.  Table  III  shows  the  progress 
of  germination  from  time  to  time. 

Table  III. 

Comparative  Germination  of  Large  and  Small  Seeds  Sown  April  5th. 


Description 

Germination 

Number 

Per  cent. 

May 
1 

May 
8 

May 
IS 

May 
22 

May 
1 

May 
8 

May 
IS 

May 
22 

Large  

Small  

42 

43 

131 
145 

133 
150 

134 
153 

14 
14-3 

43-6 
48.3 

44-3 
50 

44.6 
51 

From  the  tables  and  figures  it  is  at  once  evident  that  there  is 
practically  no  difference  in  germination  due  to  size.  In  this  par- 
ticular case  the  advantage  even  lies  with  the  small  seeds,  though  the 


488  The  Germination  of  Belladonna  Seed.  {XveZ^r^u"1' 

margin  is  so  small  that 'it  can  hardly  be  taken  to  indicate  that  such  is 
always  the  case.  It  appears,  then,  that  the  small  seeds  are  in  no  wise 
inferior  to  the  larger  ones  in  so  far,  at  least,  as  concerns  the  ger- 
mination. What  the  relative  growth  and  development  of  these  plants 
will  be  is  an  entirely  different  problem.  There  was  little  to  choose, 
between  them  seven  weeks  after  sowing.  However,  any  inferiority 
due  to  seed  would  very  likely  not  become  evident  until  later  in  the 
plant's  development.  A  careful  study  is  being  made  of  this  phase 
of  the  problem  with  special  reference  to  the  relation  of  the  size 
of  the  seed  to  the  development  of  alkaloids  in  the  plants  grown 
therefrom.  It  is  interesting  to  note  that  the  progress  of  the  ger- 
mination is  very  similar  in  the  two  kinds  of  seeds,  as  Figure  2  plainly 
shows. 

Relation  of  Weight  of  Seed  to  Germination. 

While  the  size  of  the  seed  was  found  to  have  nothing  to  do  with 
the  germinating  power,  the  question  of  the  weight  of  the  seed  prom- 
ised to  be  of  greater  importance.  Like  most  other  seeds,  a  consider- 
able percentage  of  belladonna  seed  is  much  lighter  than  the  average. 
It  is  a  question  of  specific  gravity,  there  being  no  relationship  as  to 
size.  In  order  to  determine  the  percentage  of  the  seed,  which  is 
generally  found  to  be  inferior  as  to  weight,  a  method  of  separating 
the  light  from  the  heavy,  based  on  the  specific  gravity  of  the  seed, 
was  used,  which  was  briefly  as  follows:  10  Gms.  of  seeds  previously 
cleaned  from  husks  and  all  inert  matter  are  thrown  into  a  tall,  lipped 
beaker  of  1  litre  capacity  and  half  full  of  water.  After  thorough 
stirring  to  enable  all  the  seeds  to  become  wet,  the  water  is  brought  to 
a  stop  and  the  heavy  seeds  allowed  to  settle  on  the  bottom,  while  the 
light  ones  remain  on  or  near  the  surface.  The  latter  are  then  care- 
fully decanted  into  a  Gooch  crucible  (the  perforations  in  such  a 
crucible  are  just  small  enough  to  prevent  the  seeds  from  going 
.  through)  attached  to  a  vacuum  flask.  With  a  strong  current  of  air 
pulling  through  the  crucible  and  occasional  stirring  the  seeds  are 
soon  dry  and  can  then  be  weighed.  The  heavy  seeds  are  filtered  off 
and  dried  in  a  similar  way.  According  to  this  method,  six  10-gramme 
portions  from  one  general  lot  of  seeds  were  separated  into  the  light 
and  heavy  portions  to  determine  the  accuracy  of  the  method.  The 
volume  of  each  portion  was  determined  by  placing  the  seeds  in  a 


Tovember^ST1*}    7  he  Germination  of  Belladonna  Seed.  489 

tall  and  very  narrow  graduated  cylinder  containing  about  1  Cc. 
to  the  inch,  and  the  scale  divided  into  tenths.  Table  IV  summarizes 
the  result. 


Table  IV. 

Relative  Per  Cent,  of  Light  and  Heavy  Seed  in  a  General  Lot  Formed  by  Separation 
According  to  Specific  Gravity. 


Portion 

Light 

Heavy- 

Weight 

Volume 

Weight 

Volume 

Gms. 

Per  cent. 

Cc. 

Per  cent. 

Gms. 

Per  cent. 

Cc. 

Per  cent. 

I 

8.25 

82.5 

16. 1 

84-3 

i-75 

17-5 

3-0 

15-7 

2 

7.81 

78.1 

15-5 

81.6 

2.19 

21.9 

3-5 

18.4 

3 

8.12 

81.2 

16.1 

84.7 

1.88 

18.8 

2.9 

15-3 

4 

8-53 

85-3 

17.2 

88.2 

1.47 

14.7 

2-3 

11. 8 

5 

8.68 

86.8 

17.4 

88.4 

1.32 

13.2 

2.3 

11.6 

6 

8.05 

80.5 

15.8 

82.3 

i-95 

19-5 

34 

17.7 

Average 

8.24 

82.4 

16.35 

84.9 

1.76 

17.6 

2.9 

151 

The  results  show  that  the  method  of  separation  is  fairly  accurate 
within  certain  limits.  Seeds  from  five  individual  plants  were  then 
separated  according  to  the  method  just  described,  with  the  results 
as  shown  in  Table  V. 

Table  V. 


Proportion  of  Light  and  Heavy  Seed  from  Five  Individual  Plants. 


Light 

Heavy 

Number 

of 

Weight 

Volume 

Weight 

Volume 

plant 

Gms. 

Per  cent. 

Cc. 

Per  cent. 

Gms. 

Per  cent. 

Cc. 

Per  cent. 

15 

6.26 

62.6 

11.6 

65.2 

374 

374 

6.2 

34-8 

47 

546 

54-6 

10.9 

58.9 

4-54 

454 

7.6 

41. 1 

4i 

7.98 

79.8 

16.0 

847 

2.12 

21.2 

3-o 

15-3 

I  IW 

7.90 

79.0 

154 

837 

2.10 

21.0 

3-0 

16.3 

14 

5-34 

534 

10. 0 

56.2 

4.66 

46.6 

7.8 

43-8 

There  appears  to  be  a  considerable  difference  in  the  proportion 
of  light  and  heavy  seeds  in  the  above  individuals,  while  in  all  of  them 
the  proportion  of  heavy  seeds  is  considerably  greater  than  in  the 


490  The  Germination  of  Belladonna  Seed.  { ^oveSr^S5" 

general  lot  used  in  testing  the  method  of  separation.  Table  VI  shows 
the  weight  of  500  of  the  light  and  the  heavy  seeds  from  the  five 
individual  plants. 


Table  VI. 

Weight  of  500  Each  of  Light  and  Heavy  Seeds  from  Individual  Plants. 


Description 

Weight  (Gms.) 

No.  15 

No.  47 

No.  41 

No.  nw 

No.  14 

Light  

Heavy  

O.4606 
0.5I05 

O.4IOI 
O.461 1 

0-4757 
O.5288 

O.5161 
O.561O 

O.4409 
O.4646 

To  test  the  relative  germinating  power  of  the  light  and  heavy 
seeds,  fifty  of  each  were  sown  in  five  different  pots,  one  for  each 
of  four  individual  plants.  Table  VII  shows  the  germination  at 
various  stages. 


Table  VII. 

Relative  Germination  of  Light  and  Heavy  Seeds  from  Four  Individual  Plants.  Seeds 

Sown  April  13th. 


Number 
of  plant 

Description 
of  seed 

Germination 

Num 

ber 

Per  cent. 

May  8 

May  15 

May  22 

May  29 

May  8 

May  15 

May  22 

May  29 

47  { 

Light 

3 

7 

7 

8 

6 

14 

14 

16 

Heavy 

19 

24 

24 

24 

38 

48 

48 

48 

4i  | 

Light 

3 

5 

5 

5 

6 

10 

10 

10 

Heavy 

3 

8 

12 

14 

6 

16 

24 

28 

IIW  | 

Light 

4 

5 

5 

6 

8 

10 

10 

12 

Heavy 

9 

21 

24 

26 

18 

42 

48 

52 

-  { 

Light 

0 

1 

I 

0 

2 

2 

2 

Heavy 

27 

3i 

32 

32 

54 

62 

64 

64 

The  results  show  conclusively  that  the  light  seed  is  mostly  dead, 
only  a  small  percentage  of  it  germinating.  Figure  3  shows  graphi- 
cally the  progressive  germination  in  each  case. 


Relation  of  Color  of  the  Seed  to  the  Germination. 
Belladonna  seeds  are  either  of  a  rich  brown  or  silver  gray  color. 
That  a  relationship  might  exist  between  color  and  weight  was  con- 


Xv^XeV^iT1"}    The  Germination  of  Belladonna  Seed.  491 


492 


The  Germination  of  Belladonna  Seed.    {  ^Vembe/iSi"' 


sidered  probable,  and  for  that  reason  the  lots  of  500  seeds  each  used 
to  determine  the  relative  weights  of  light  and  heavy  seeds  as  given 
in  Table  VI  were  separated  into  the  brown  and  gray,  with  the 
following  result : 


Table  VIII. 

Relative  Number  of  Brown  and  Gray  Seed  A  mong  the  Light  and  Heavy  Seed  from 

Five  Individual  Plants. 


Light 

Heavy 

Number 

of 

Brown 

Gray 

Brown 

Gray 

plant 

Number 

Per  cent. 

Number 

Per  cent. 

Number 

Per  cent. 

Number 

Per  cent. 

15 

37 

7-4 

463 

92.6 

387 

77-4 

113 

22.6 

47 

397 

794 

IO3 

20.6 

471 

94.2 

29 

5-8 

4i 

86 

17.2 

414 

82.8 

39 

7.8 

461 

92.2 

14 

460 

92.0 

40 

8.0 

500 

100 

0 

0.0 

IIW 

65 

13.0 

435 

87.0 

241 

48.2 

259 

51.8 

Average 

209 

41.8 

291 

58.2 

328 

65.6 

172 

34-4 

Evidently  there  is  no  definite  relation  between  color  and  weight, 
as  the  results  show  a  great  variation.  According  to  the  average,  it 
appears  that  the  heavy  seeds  contain  a  noticeably  larger  percentage 
of  brown  ones  than  the  light  seeds.  From  this  one  would  judge  that 
the  brown  seeds  are  of  a  better  quality  and  would  show  a  greater 
percentage  of  germination.  To  determinate  whether  such  is  the 
case,  100  seeds  of  the  two  colors  were  sown  in  pots  on  April  13th, 
with  the  result  as  indicated  in  Table  IX  following. 

Table  IX< 

Relative  Germination  of  Brown  and  Gray  Seeds  Sown  April  ijth. 


Germination 

Description 

May  8 

May  15 

May  22 

May  29 

Per  cent. 

Per  cent. 

Per  cent. 

Per  cent. 

13 

28 

42 

45 

Gray  

28 

42 

53  . 

56 

These  results  are  quite  contrary  to  what  was  expected.  Table 
VIII  shows  that  the  heavy  seed  from  plant  No.  14  contained  no 
grays  whatever,  while  the  light  seed  from  the  same  plant  was  almost 
all  gray.    Reference  to  Figure  3  shows  that  the  heavy  seed  ger- 


494 


The  Germination  of  Belladonna  Seed.  {A™ovJmberPi9i?' 


minated  much  better  than  the  light.  From  this  it  would  seem  to  follow 
that  the  brown  seeds  were  much  superior  to  the  grays,  but,  in  view 
of  the  results  obtained  from  the  test,  it  must  be  concluded  that  there 
is  no  definite  relation  between  the  color  and  the  germinating  power. 
Figure  4  will  serve  to  bring  out  more  clearly  the  results  of  the  test. 


Fig.  5. — Plants  from  300  large  belladonna  seeds  seven  weeks  after  sowing. 

Treatment  of  the  Seeds  with  Suephuric  Acid. 

Probably  the  most  striking  and,  at  the  same  time,  most  undesir- 
able characteristic  of  the  germination  of  belladonna  seed  is  the  lack 
of  uniformity  it  displays.    The -first  seeds  usually  begin  to  ger- 


A™ovimb4rf loiT* }    The  Germination  of  Belladonna  Seed.  495 

minate  in  about  three  weeks  after  sowing.  The  bulk  of  the  seeds 
germinate  between  the  fourth  and  fifth  week.  After  that  the  progress 
is  slow,  a  few  per  cent,  of  the  total  appearing  every  week  for  probably 
several  months.  Figure  5  illustrates  this  lack  of  uniformity  in  germi- 
nation. 

It  has  often  been  observed  that  new  plants  will  appear  after 
the  others  sown  at  the  same  time  are  seven  to*  eight  inches  high.  In 
some  cases  this  might  be  due  to  lack  of  uniformity  in  sowing  as 
regards  character  and  condition  of  soil  and  depth  of  soil  covering 
the  seed.  This  might  be  especially  true  when  sowing  in  the  field. 
In  greenhouse  work,  however,  such  conditions  are  generally  avoided, 
and  a  different  explanation  must  be  found.  It  was  thought  that 
possibly  these  slowly  germinating  seeds  might  be  what  are  generally 
known  as  "  hard-heads,"  that  is,  seeds  with  such  heavy  outer  walls 
that  the  necessary  warmth  and  moisture  essential  to  germination  can 
penetrate  but  slowly.  It  is  well  known  that  with  such  seeds  ger- 
mination can  sometimes  be  hastened  by  treating  them  with  some 
substance  like  strong  corroding  acids  that  will  partly  disintegrate 
the  outer  covering  of  the  seed.  Such  treatment,  of  course,  is  fatal 
if  allowed  to  go  too  far. 

Miller  1  found  concentrated  sulphuric  acid  beneficial  when  applied 
for  a  period  ranging  from  five  to  fifteen  minutes,  the  ten-minute 
application  giving  by  far  the  best  results.  He  does  not  state,  however, 
the  actual  percentage  of  germination  obtained  by  means  of  the 
treatment.  T.  B.  Young  found  a  five-minute  treatment  with  concen- 
trated sulphuric  acid  very  beneficial,  but  concluded  that  a  ten- 
minute  treatment  would  be  too  long.  Here  again  data  as  to  the 
actual  percentage  of  germination  are  not  available. 

To  obtain  further  information  on  this  subject,  belladonna  seed 
was  subjected  to  sulphuric  acid  of  various  strengths  and  for  various 
periods  as  shown  in  Table  X. 

A  convenient  quantity  of  seeds  were  treated  for  the  required 
length  of  time  with  acid  of  the  desired  strength  in  a  small  beaker 
and  then  quickly  transferred  to  a  Gooch  crucible  attached  to  a  vacuum 
flask  and  rapidly  and  repeatedly  washed  with  water.  They  were 
then  dried  by  pulling  air  through  the  crucible. 

To  determinate  the  relative  germination  of  these  treated  seeds, 


1  Miller,  Fred  A.,  "  The  Propagation  of  Medical  Plants,"  Bulletin  of  the 
Torrey  Botanical  Club,  vol.  41,  No.  2,  pp.  105-136. 


496 


The  Germination  of  Belladonna  Seed. 


Am.  Jour.  Pharm. 
November,  1914. 


Table  X. 

Showing  Strength  of  Acid  Used,  Time  of  Treatment,  and  Designation  of  the  Seed 

in  Each  Case. 


■  Strength 

Time  treated 

of  acid 

Per  cent.* 

1  minute 

10  minutes 

30  minutes 

60  minutes 

92.5 

Ai 

A2 

A3 

A4 

75 

B2 

B3 

B4 

50 

d 

c2 

c3 

c4 

25 

Di 

D2 

D3 

D4 

By  volume. 


Table  XI. 

Relative  Germination  of  Seeds  Treated  with  Sulphuric  Acid  and  Sown  on  March  31st. 


Germination 


Number 

Percentage 

4-24 

5-1 

5-8 

5-15 

5-22 

4-24 

s-i 

5-8 

s-15 

5-22 

Ai  

I 

7 

26 

29 

32 

1.66 

11.6 

43-3 

48.3 

53-3 

A2  

9 

22s 

35 

35 

35 

15.0 

36.6 

58.3 

58.3 

58.3 

A3  

2 

3 

3 

3 

3 

3-3 

5-0 

5-0 

5-0 

5-0 

A4  

0 

0 

0 

0 

0 

0 

0 

0 

0 

0 

Total .  . 

12 

33 

65 

68 

70 

5i- 

17,8 

27.1 

28.3 

29.2 

Bi  

0 

4 

24 

26 

29 

0 

6.6 

40.1 

43-3 

48.3 

B2  

11 

34 

34 

34 

1.66 

18.3 

56.6 

56.9 

56.6 

B3  

5 

14 

30 

30 

30 

8-3 

23-3 

50- 

50. 

50. 

B4  

0 

2 

3 

3 

3 

0 

3-3 

5- 

5- 

5- 

Total .  . 

6 

3i 

9i 

93 

96 

2-5 

13- 

37-9 

38.7 

40. 

Ci  

0 

2 

26 

34 

39 

0 

3-3 

43-3 

56.6 

65. 

c2  

0 

9 

37 

38 

41 

0 

15- 

61.6 

63-3 

68.3 

c3  

0 

5 

26 

3i 

3i 

0 

8-3 

43-3 

51-6 

51-6 

c4  

0 

2 

19 

23 

24 

0 

3-3 

31.6 

38.3 

40. 

Total .  . 

0 

18 

108 

126 

135 

0 

7-5 

45 

52.5 

56.2 

Dx  

0 

4 

26 

26 

26 

0 

6.6 

43-3 

48.3 

48.3 

D2  

0 

4 

25 

28 

28 

0 

6.6 

41.6 

46.6 

46.6 

D3  

0 

6 

34 

36 

36 

0 

10. 

56.6 

60. 

60. 

D4  

0 

7 

25 

25 

26 

0 

n,6 

41.6 

41.6 

48.3 

Total .  . 

0 

21 

1 10 

115 

116 

0 

8-75 

45-8 

47-9 

48.3 

^Vember^oiT1'}    The  Germination  of  Belladonna  Seed. 


497 


sixty  of  each  were  placed  in  pots  on  March  31st.  Table  XI  shows  the 
result. 

These  results  seem  to  demonstrate  a  number  of  facts.  The 


Fig.  6. — Curves  showing  comparative  germination  of  all  seeds  treated  with  sulphuric  acid 
of  02.5  per  cent.  (A),  75  per  cent.  (B),  50  per  cent.  (C),  and  25  per  cent.  (£>).  Seeds  were  sown 
March  31st. 

effect  of  the  acid  treatment  as  conducted  in  this  experiment  is  of  little 
practical  value,  the  only  benefit  derived  being  that  of  a  slight  accele- 
ration in  germination.  The  total  germination  is  not  found  to  be 
any  greater,  on  the  whole,  than  in  the  case  of  seeds  not  subjected 


498  The  Germination  of  Belladonna  Seed,    j  A^*f£ v^lm' 

to  the  treatment.  It  is  evident  that  contact  with  concentrated  (92.5 
per  cent.)  sulphuric  acid  destroys  the  germinating  power  almost 
completely  if  continued  longer  than  ten  minutes.  Treatment  with 
75  per  cent,  acid  may  be  continued  for  thirty  minutes  without  injury, 
which  is  also  true  of  the  50  per  cent.  acid.  When  the  acid  is  below 
50  per  cent,  the  time  of  contact  up  to  one  hour  seems  to  be  imma- 
terial. It  is  noteworthy  that  only  the  seeds  treated  with  concentrated 
and  75  per  cent,  acid  showed  any  germination  on  April  24th,  twenty- 
four  days  after  sowing.  In  the  following  week,  however,  the  seeds 
which  received  treatment  with  the  50  and  25  per  cent,  acids  showed 
about  the  same  germination  as  the  others,  and  from  then  on  they 
continued  to  show  to  better  advantage. 

In  order  to  indicate  more  clearly  what  concentration  of  acid 
and  what  length  of  treatment  are  the  most  desirable,  the  data  are 
arranged  in  the  following  tables. 


Table  XII. 

Total  Germination  of  all  Seeds  Treated  with  92.5,  75,  50,  and  25  Per  Cent.  Sulphuric 
A  cid  for  Different  Lengths  of  Time. 


Treatment 

Germination 

Number 

Per  cent. 

4-24 

5-1 

5-8 

5-15 

5-22 

4-24 

5-1 

5-8 

5-15 

5-22 

A1A2A3A4 . 

12 

33 

65 

68 

70 

5 

17.8 

27.1 

28.3 

29.2 

B1B2B3B4 . 

6 

31 

91 

93 

96 

2-5 

13 

37-9 

38.7 

40. 

C1C2C3C4 . 

0 

18 

108 

126 

135 

O 

7-5 

45 

52.5 

56.2 

DiD2D3D4 

0 

21 

no 

115 

116 

0 

8-75 

45-8 

47-9 

48.3 

Table  XIII. 


Total  Germination  of  all  Seeds  Treated  for  1,  10,  30,  and  60  Minutes  with  Sulphuric 

Acid  of  Various  Strengths. 


Germination 


Treatment 

Number 

Per  cent. 

4-24 

5-1 

5-8 

5-15 

5-22 

4-24 

5-1 

5-8 

5-15 

5-22 

AxBidDx 

I 

17 

102 

115 

126 

O.4 

7- 

42.5 

47-9 

52.5 

A2B2C2D2 

IO 

46 

131 

135 

138 

4.2 

19.2 

54-6 

56.2 

57-5 

AsBsCsDs 

7 

28 

93 

100 

100 

2.9 

II.7 

38.7 

41.7 

4i>7 

A4B4C4D4 

0 

11 

47 

5i 

53 

0.0 

4.5 

19.5 

21.2 

22.1 

A.m.  .Tour.  Pharm. 
November,  1914. 


The  Germination  of  Belladonna  Seed'. 


499 


Treatment  of  Seeds  with  Hydrogen  Peroxide. 
It  has  been  found  that  hydrogen  peroxide  has  an  accelerating 
influence  on  the  germination  of  a  large  number  of  seeds,  and  for 
that  reason  the  following  experiment  was  undertaken  to  determine 


Fig.  7. — Curves  showing  comparative  germination  of  all  seeds  treated  with  sulphuric  acid 
for  1  minute  (1),  10  minutes  (2),  30  minutes  (3),  and  60  minutes  (4).  Seeds  were  sown  March 
3ist. 

whether  belladonna  seed  yielded  to  such  treatment.  The  hydrogen 
peroxide  used  was  the  commercial  kind  containing  40  per  cent,  of 
absolute  peroxide.    This  strength  is  designated  in  the  tabulations 


500  The  Germination  of  Belladonna  Seed.  {^ovemberfilS1' 

as  100  per  cent.  The  weaker  solutions  designated  as  80,  60,  40,  and 
20  per  cent,  in  the  tabulations  were  made  by  diluting  the  commercial 
material  on  the  basis  of  100  per  cent.  A  small  lot  of  the  seeds  was 
treated  with  the  various  solutions  of  peroxide  for  18  hours.  The 
treatment  was  duplicated  with  another  lot  of  seeds  for  24  hours  and 
with  still  another  lot  for  48  hours.  All  seeds  were  immediately  dried 
after  the  removal  of  the  peroxide  in  a  Gooch  crucible.  One  hundred 
seeds  of  each  lot  were  planted  on  February  16th  and  the  germination 
noted  from  time  to  time.  Table  XIV  shows  the  percentage  of  ger- 
mination in  each  case  up  to  April  9th,  when  the  germination  appeared 
to  be  completed. 

Table  XIV. 


Comparative  Germination  of  Seeds  Treated  with  Hydrogen  Peroxide  and  Sown  ' 

February  16th. 


Time  of  treatment 

Strength 
of 

hydrogen 

Percentage  of  germination 

peroxide 

used  per 
cent. 

March  13 

March  19 

March  25 

April  2 

April  9 

20 

II 

31 

32 

34 

35 

40 

18 

56 

60 

64 

64 

1 8  hours  < 

60 

19 

63 

66 

69 

69 

80 

13 

6l 

62 

65 

67 

100 

14 

29 

35 

40 

4i 

20 

32 

52 

58 

59 

59 

40 

22 

60 

68 

70 

70 

24  hours  < 

60 

18 

39 

48 

52 

52 

80 

28 

36 

40 

44 

44 

100 

27 

39 

40 

44 

45 

20 

17 

4i 

49 

50 

55 

40 

12 

24 

29 

34 

39 

48  hours  ■ 

60 

34 

54 

55 

60 

60 

80 

23 

49 

53 

55 

56 

100 

16 

37 

39 

43 

44 

Table  XV, 

Total  Number  Germinated  of  all  Seeds  Treated  for  18,  24,  and  48  Hours,  Respectively. 


Time  of  treatment 

Number  of  s 

eeds  germinated  out  of  500 

March  13 

March  19 

March  25 

April  2 

April  9 

1 8  hours  

75 

240 

255 

272 

276 

24  hours  

127 

226 

254 

269 

270 

48  hours  

102 

205 

225 

242 

2-54 

Am.  Jour.  Pharm. 
November,  1914. 


j   The  Germination  of  Belladonna  Seed. 


5oi 


Figures  8  and  9  show  graphically  the  effect  of  the  treatment  with 
peroxide,  both  as  to  the  strength  of  the  solution  used  and  the  time 
of  treatment. 


FlG.  8. — Curves  showing  the   comparative  germination   of   all   seeds  treated   with  hydrogen 
peroxide  of  20,  40,  60,  80,  and  100  per  cent,  strength.    Seeds  sown  on  February  16th. 

It  is  evident  that  the  treatment  with  hydrogen  peroxide  is  of  very 
appreciable  benefit.  The  percentage  of  germination  during  the  first 
four  or  five  weeks,  when  compared  with  that  of  the  untreated  seeds 


502  The  Germination  of  Belladonna  Seed.    { ^vimberfm?' 

used  as  a  check,  is  much  greater  than  was  expected.  •  It  appears,  from 
the  check,  that  this  lot  of  seeds  would  be  especially  slow  in  germinat- 
ing under  ordinary  conditions,  though  the  total  germination  would 

7o 


63 

6t> 


Fig.  g. — Curves  showing  the  comparative  germination  of  all  seeds  treated  with  hydrogen  per- 
oxide for  1 8,  24,  and  48  hours.    Seeds  sown  February  16th. 


probably  compare  favorably  with  the  usual  average.  The  maximum 
germination  secured  by  the  peroxide  treatment  was  70  per  cent., 
while  the  minimum  was  35  per  cent.    Taken  as  a  whole,  the  effect 


Am  Jour.  Pharm. 
November,  1914. 


The  Germination  of  Belladonna  Seed. 


503 


of  the  peroxide  seems  to  have  been  to  induce  a  uniformity  in  the 
germination  rather  than  an  acceleration  or  an  actual  increase  in 
percentage.  From  these  experiments  and  from  those  with  sulphuric 
acid  it  seems  that  when  working  under  conditions  such  as  those 
described  the  effect  of  treating  the  seeds  with  chemicals  is  to  induce 
a  uniformity  or  spontaneity  in  the  germination.  The  seeds,  however, 
seem  to  require  as  much  time  to  begin  germination  as  the  untreated 
seeds. 

As  regards  the  concentration  of  the  peroxide  used,  it  is  evident 
that  neither  the  concentrated  nor  the  greatly  diluted  material  is  of 
as  much  benefit  as  the  medium  strengths.  Tt  will  be  seen  from 
Figure  8  that  the  60  per  cent,  solution  gave  the  best  results.  The 
80  and  40  per  cent,  solutions  gave  results  very  much  alike,  while  the 
20  and  100  per  cent,  solutions  had  the  least  effect. 

The  time  of  treatment  does  not  seem  to  make  any  great  difference. 
The  18-  and  24-hour  treatment  gave  very  similar  results,  while  the 
48-hour  treatment  was  not  quite  so  effective.  It  is  evident  that  there 
is  no  benefit  in  treating  the  seeds  longer  than  18  hours,  and  it  is 
possible  that  a  shorter  period  would  be  just  as  effective. 

The  Effect  of  Scratching  the  Seed  Coats. 
Many  seeds  germinate  very  slowly,  owing  to  their  hard  and 
thick  coats,  which  do  not  admit  of  a  rapid  permeation  of  moisture 
and  air  into  the  seed.  Such  seeds  have  often  been  benefited  by 
scratching  the  surface  by  some  mechanical  means,  so  as  to  hasten  the 
absorption  of  moisture,  with  a  consequent  acceleration  of  the  ger- 
mination. 

To  determine  the  effect  of  such  methods  on  belladonna  seeds,  a 
quantity  of  the  seed  was  shaken  in  a  bottle  with  powdered  glass  for 
one  and  a  half  hours.  Another  quantity  was  rubbed  gently  between 
two  sheets  of  fine  emery  paper.  One  hundred  seeds  from  each  lot 
were  planted  as  a  test.   The  following  table  shows  the  result : 

Table  XVI. 

Comparative  Germination  of  Belladonna  Seed  Scratched  with  Powdered  Glass  and 
Emery  Paper.   Seeds  Sown  February  16th. 


Treatment  of  seed 

Percentage  of  germination 

March  13 

March  19 

March  25 

April  2 

April  9 

April  16 

Check  (untreated) . . . . :  

2 

3 

5 

•  l6 

25 

33 

Shaken  with  powdered  glass . 

3 

18 

21 

34 

45 

47 

Rubbed  with  emery  paper. .  . 

0 

1 1 

17 

22 

26 

28 

504 


The  Germination  of  Belladonna  Seed. 


|  Am.  Jour.  Pharm. 
\   November,  1914. 


The  effect  of  scratching  does  not  appear  to  be  as  great  as  was 
expected.  The  shaking  with  sand  gave  better  results  than  the  emery 
treatment.    Figure  10  shows  the  results  graphically. 

74  

64  \ 
6o 


So 


Fig.  io. — Curves  showing  effect  of  scratching  seed  coats.    (A)  Seeds  shaken  with  powdered 
glass;   (B)  seeds  rubbed  between  emery  paper;   (C)  check.    Seeds  sown  February  i6th. 


Summary. 

The  subjection  of  belladonna  seed  to  freezing  temperatures 
accelerates  their  germination.  Hence  it  is  of  benefit  to  sow  the 
seed  in  the  fall  in  order  to  insure  a  rapid  and  early  germination  in 
spring. 


^emteVPi9i4m'}    The  Germination  of  Belladonna  Seed.  505 

There  appears  to  be  no  relationship  between  the  size  of  the  seed 
and  its  germinating  power.  This  must  not  be  taken  to  indicate  that 
a  relationship  does  not  exist  between  the  size  of  the  seed  and  the  vigor 
and  strength  of  the  plant. 

The  heavy  seeds  are  by  far  the  best.  The  percentage  of  ger- 
mination of  the  light  seeds  is  very  small.  Separation  of  these  inert 
seeds  can  be  readily  effected  by  immersing  the  seed  in  water  and  dis- 
carding those  which  do*  not  sink.  The  proportion  of  light  and  heavy 
seed  from  each  individual  plant  varies  greatly.  This  may  be  due 
partly  to  carelessness  in  picking  the  berries,  as  unripe  berries  contain 
light  and  worthless  seeds.  The  question  of  drying  is  also  of  impor- 
tance. The  berries  must  be  thinly  scattered  and  dried  in  a  well- 
ventilated  room,  in  order  to  reduce  molding  to  a  minimum.  It  is 
probable  that  a  certain  percentage  of  the  seed  in  a  fully  developed 
berry  is  inert,  which  would  account  to  some  extent  for  the  relatively 
low  percentage  of  germination  of  the  average  belladonna  seed. 

Color  appears  to  be  no  criterion  of  the  value  of  the  seed  as 
regards  germinative  power.  The  brown  seeds  have  a  better  appear- 
ance, but  apparently  the  gray  ones  have  equal  vitality. 

While  other  investigators  have  found  that  treatment  with  con- 
centrated sulphuric  acid  from  one  to  ten  minutes  is  of  benefit,  experi- 
ments with  various  strengths  of  acid  for  periods  ranging  from  one 
to  sixty  minutes  showed  that,  as  a  whole,  the  treatment  is  not  of  any 
great  value.  The  germination  was  accelerated  in  some  instances,  but 
no  material  increase  in  actual  germination  was  noted. 

Treating  seeds  with  hydrogen  peroxide  was  found  to  be  of  very 
material  benefit.  Eighteen  and  twenty-four  hours  gave  better  results 
than  longer  treatment.  A  60  per  cent,  solution  of  the  commercial 
hydrogen  peroxide  gave  the  best  results.  The  concentrated  solution 
was  the  least  beneficial. 

Scratching  the  seed  coats  by  shaking  in  a  bottle  with  powdered 
glass  and  by  rubbing  between  sheets  of  emery  paper,  while  of  some 
benefit,  was  not  nearly  as  beneficial  as  the  peroxide  treatment. 


506 


Medicinal  Plant  Gardens. 


(  Am.  Jour.  Pharm. 
I   November,  1914. 


MEDICINAL  PLANT  GARDENS.* 

By  Dr.  W.  W.  Stockberger,  Physiologist  in  Charge  of  Drug- Plant  and 
Poisonous-Plant  Investigations,  Bureau  of  Plant  Industry,  United 
States  Department  of  Agriculture. 

It  is  not  my  intention  in  this  paper  to  present  a  descriptive 
account  of  medicinal  plant  gardens  in  general,  or  even  to  discuss 
the  more  important  ones  of  this  country,  except  in  so  far  as  refer- 
ence to  them  may  be  necessary  by  way  of  illustration.  I  shall 
endeavor,  however,  to  point  out  what  to  me  appear  to  be  some 
popular  misconceptions  concerning  the  scope  and  function  of  such 
gardens,  and  to  suggest  how  they  may  be  made  to  increase  their 
usefulness  to  Materia  Medica  and  Pharmacognosy. 

For  the  purpose  of  this  discussion,  medicinal  plant  gardens 
may  be  regarded  as  falling  under  one  of  two  general  classes,  the 
first  being  pedagogic,  the  second  industrial.  The  pedagogic  garden 
is,  naturally,  an  adjunct  of  a  school  of  pharmacy  or  of  a  botanic 
garden.  Its  scope  includes  all  medicinal  plants  that  are  adapted  to 
existing  soil  and  climatic  conditions,  supplemented  by  greenhouse 
facilities.  Its  function  is  to  familiarize  students  with  the  habit  and 
appearance  of  the  entire  living  plant,  some  part  of  which  is  used 
as  a  plant  drug,  to  supply  the  need  for  authentic  specimens  for 
observation  and  demonstration  in  the  classroom,  and  to  furnish 
materials  for  research  work  on  the  morphology  and  chemical  con- 
stituents of  drug  plants.  Necessarily  it  will  be  found,  desirable  to 
grow  a  large  number  of  species  in  this  type  of  garden,  but,  owing 
to  the  cost  of  maintenance,  the  space  which  can  be  devoted  to  any 
one  species  will  be  very  small. 

The  industrial  garden,  on  the  other  hand,  is  an  adjunct  of  public 
or  private  enterprise,  the  object  of  which  is  to  give  additional  infor- 
mation concerning  our  agricultural  resources.  Its  scope  is  the  same 
as  that  of  the  pedagogic  garden,  but  it  differs  very  materially  in 
function,  which  is  to  serve  for  the  determination  of  the  adaptability 
of  medicinal  plants,  not  only  to  soil  and  climatic  conditions,  but 
to  economic  conditions  as  well.  In  the  industrial  garden  a  large 
number  of  species  will  be  tested  on  a  small  scale  to  determine 
whether  the  soil  and  climate  are  suitable  for  their  growth ;  then  the 

*  A  paper  read  before  the  Scientific  Section  of  the  A.  Ph.  A.  at  the 
Detroit  meeting,  1914. 


Am.  Jour.  Pharm.  ) 
November,  1914.  J 


Medicinal  Plant  Gardens. 


507 


few  promising  ones  must  be  tried  out  on  an  area  large  enough  to 
yield  reliable  data  on  the  actual  conditions  of  commercial  produc- 
tion. A  considerable  acreage  of  land  is  indispensable  for  this  type 
of  garden  if  the  results  secured  therein  are  expected  to  have  much 
economic  significance. 

There  is  no  lack  of  evidence  that  the  general  public  often,  if 
not  as  a  rule,  fails  to  differentiate  the  functions  of  the  pedagogic 
and  industrial  gardens,  since  advice  is  freely  sought  from  both  re- 
garding the  production  of  medicinal  plants  for  the  sole  purpose  of 
deriving  profit  therefrom.  It  is  also  an  open  question  whether  this 
distinction  in  function  is  in  every  case  clearly  understood  by  those 
responsible  for  the  management  of  medicinal  plant  gardens.  State- 
ments sometimes  unguarded,  or  not  properly  qualified,  and  some- 
times based  upon  inconclusive  and  insufficient  data,  have  on  several 
occasions  inspired  the  imagination  of  writers  for  the  popular  maga- 
zines or  daily  press,  and,  as  a  result,  visions  of  large  and  easy  profits 
have  been  portrayed  under  various  alluring  titles,  as,  for  example, 
"  Big  Profit  from  Drug  Weeds,"  "  The  Herb  Grower  Has  a  Chance 
at  an  $18,000,000  Business,"  "  A'  Profit  of  One  Hundred  Dollars 
per  Acre  from  Growing  Medicinal  Weeds."  Moreover,  the  wide- 
spread interest  in  the  possibility  of  growing  medicinal  plants  for 
profit  which  has  been  developed  in  this  country  during  the  past 
decade  has  been  capitalized  by  a  number  of  crafty  promoters, 
who  use  the  mails  and  the  columns  of  journals  and  magazines  to 
disseminate  flamboyant  advertisements  of  the  enormous  profits 
which  may  be  made  by  growing  certain  medicinal  plants.  Frequently 
the  name  of  the  plant  is  withheld  until  the  victim  has  remitted  from 
one  to  five  dollars,  for  which  he  receives  practically  valueless  instruc- 
tions for  the  cultivation  of  some  plant  poorly  adapted  to  our  eco- 
nomic conditions.  A  typical  get-rich-quick  scheme  of  this  class  is 
explained  thus :  "It  has  to  do  with  a  certain  plant  which  grows 
like  a  weed ;  it  is  cut  and  cured  like  hay  and  sells  for  45  cents  per 
pound,  which  is  at  the  rate  of  $900  per  ton."  The  investment  of 
one  dollar  brings  the  name  of  the  herb,  with  the  further  information 
that  the  product  of  one  acre  will  sell  for  $1800!  As  a  matter 
of  fact,  the  commercial  cultivation  of  this  plant  is  almost  unknown 
in  the  United  States,  and  there  is  yet  no  established  market  for  the 
American  product. 

These  illustrations  will  account  for  the  doubt  which  has  arisen 


5o8 


Medicinal  Plant  Gardens. 


f  Am.  Jour.  Pharm. 
\  November,  1914. 


in  my  mind  as  to  the  propriety  of  purely  pedagogic  gardens  being 
used  as  a  basis  for  generalizing  on  the  question  of  drug  growing 
for  profit.  In  agricultural  experimentation  it  is  well  recognized 
that  the  results  from  small  trial  plots  must  be  interpreted  with  due 
regard  for  the  large  factor  of  error,  which  is  always  present.  With 
proper  care  and  attention  it  is  relatively  easy  to  grow  a  luxuriant 
crop  of  any  one  of  a  number  of  drug  plants  on  a  square  rod  of 
good  garden  soil,  but  what  can  be  done  under  ordinary  agricultural 
conditions  on  one  or  more  acres  can  not  be  calculated  therefrom 
by  "  a  simple  sum  in  arithmetic,"  as  one  writer  has  naively  said. 

There  are  numerous  well-authenticated  instances  in  which  the 
production  of  some  medicinal  plant  has  resulted  in  a  fair  profit, 
but  there  is  yet  no  evidence  at  hand  to  justify  the  belief  that  satis- 
factory results  can  be  secured  without  some  practical  experience 
in  gardening,  some  knowledge  of  the  requirements  of  crude  drugs, 
and  due  regard  for  economic  conditions. 

Every  pharmacist  and  physician  is,  or  should  be,  interested  in 
obtaining  crude  drugs  of  highest  quality  and  standard  efficiency, 
but  material  progress  toward  the  attainment  of  this  end  will  not  be 
favored  by  encouraging  a  large  number  of  persons  to  become  small 
producers.  The  result  of  small  individual  collections,  varying  widely 
as  to  time,  place,  and  method  of  gathering,  is  seen  in  the  miscel- 
laneous aggregates  all  too  frequently  found  in  our  crude  drug 
markets,  and  unless  a  perpetuation  of  this  condition  is  desirable, 
little  encouragement  should  be  given  to  the  suggestion  that  whoever 
has  a  small  back  yard  available  may  become  a  producer  of  plant 
drugs.  1  : 

The  educational  opportunity  open  to  the  pedagogic  gardens  is 
almost  limitless.  The  dissemination  of  knowledge  to  countless 
individuals  not  having  access  to  the  garden  itself  regarding  the  his- 
tory, geographic  distribution,  methods  of  preparation,  and  uses  of 
crude  drugs  may  be  accomplished  through  illustrated  lectures  and 
carefully  prepared  articles  written  for  the  less  technical  periodicals. 
Such  misconceptions  as,  for  example,  that  the  production  of  ipecac 
in  New  England  and  vanilla  beans  in  Iowa  is  a  commercial  possi- 
bility, or  that  stramonium  is  produced  by  a  "  melon  weed,"  are  all 
too  prevalent  and  should  be  corrected.  But  educational  work  along 
this  line  deserves  little  tolerance  unless  inspired  by  some  motive 
more  commendable  than  that  of  merely  arousing  interest  in  growing 


*  Am.  Jour.  Pharm.  { 
November,  1914.  j 


Medicinal  Plant  Gardens. 


509 


drug  plants,  otherwise  the  whole  movement  will  sooner  or  later  be 
discredited.  Recently  a  reputable  pharmaceutical  journal  published 
an  article  in  which  the  writer  set  forth  at  some  length  the  possibili- 
ties for  the  commercial  production  of  a  certain  drug  plant  in  the 
Southwest.  A  request  for  further  information  brought  forth  from 
this  writer  the  astounding  statement  that  he  had  no>  personal  knowl- 
edge of  conditions  in  the  Southwest,  but,  having  grown  this  plant  in 
one  of  the  northern  States,  he  saw  no  reason  why  it  should  not  be 
profitably  grown  in  the  Southwest,  "  on  rocky  and  otherwise  unprofit- 
able land,  on  hillsides  or  arid  desert  soil."  In  this  case  the  motive  was 
evidently  merely  the  arousing  of  interest,  and  the  writer  mentioned 
displayed  a  fine  disregard  for  the  practical  difficulties  attending  the 
growing  of  the  plant  in  question,  which  sharply  localize  the  areas  on 
which  it  may  be  economically  produced. 

The  time  is  certainly  ripe  for  injecting  into  discussions  and  recom- 
mendations regarding  the  cultivation  of  medicinal  plants  some  of 
the  sanity  and  discrimination  which  characterizes  conservative  busi- 
ness operations.  Such  a  course  is  necessary  if  the  interest  already 
aroused  is  to  be  retained  and  directed  along  lines  productive  of 
beneficial  results.  It  should  be  remembered  that  the  expense  of 
agricultural  operation  varies  widely  according  to  location.  In  some 
localities  the  outlay  for  farm  labor  will  be  three  and  one-half  times 
as  much  as  in  others.  Sometimes  we  find  a  low  expense  for  labor 
associated  with  a  heavy  outlay  for  fertilizers,  sometimes  heavy 
expense  for  both  labor  and  fertilizers,  and,  again,  low  expense  for 
both.  The  complications  introduced  by  these  factors  alone  render 
it  practically  impossible  to  make  any  safe  general  statement  as  to 
the  profitableness  of  drug  growing.  Furthermore,  two  localities 
separated  by  a  distance  of  less  than  fifty  miles  may  present  a  totality 
of  conditions  so  different  that  a  drug-growing  enterprise  which  could 
probably  be  conducted  at  a  profit  in  the  one  would  with  equal  proba- 
bility fail  absolutely  in  the  other. 

I  do  not  wish  to  be  understood  as  taking  the  position  that  there 
is  no  opportunity  in  the  cultivation  of  medicinal  plants,  for  I  have 
abundant  evidence  that,  given  the  necessary  favorable  conditions,  a 
fair  return  may  be  expected  from  several  drug  crops.  On  the  other 
hand,  I  also  have  abundant  evidence  that  hundreds  of  persons  have 
received  the  impression  that  drug  crops  can  be  grown  by  anybody 
anywhere  at  a  profit  far  in  excess  of  that  to  be  obtained  from  ordi- 


510  Medicinal  Plant  Gardens.  {^ovembe/SoiT' 

nary  cultivated  crops.  I  am  convinced  that  in  some  cases  optimism 
and  enthusiasm  have  been  allowed  to  outrun  common  sense,  but  if, 
in  the  future,  due  consideration  is  given  to  the  fundamental  prin- 
ciples of  agricultural  economics,  I  believe  that  a  rational  attitude 
toward  commercial  drug-plant  cultivation  may  be  developed. 

The  founders  of  the  several  excellent  pedagogic  gardens  which 
are  now  maintained  in  connection  with  certain  schools  oi  pharmacy 
have  inaugurated  a  movement  which  promises  much  for  the  future 
of  Materia  Medica  and  Pharmacognosy.  It  is  sincerely  to  be  hoped 
that  their  example  will  lead  to  the  establishment  of  such  gardens  in 
connection  with  each  of  the  75  or  more  schools  of  pharmacy  in  the 
United  States,  and  to  an  extension  of  the  scientific  study  of  medicinal 
plants.  The  problems  demanding  attention  are  very  numerous,  but 
some  of  the  lines  of  study  and  investigation  which  need  to  be  empha- 
sized are  those  concerning  the  adaptation  and  acclimatization  of 
medicinal  plants,  the  conditions  under  which  the  active  principles  of 
plants  are  formed,  and  the  behavior  of  the  plants  themselves  under 
varying  conditions  of  climate  and  culture.  Moreover,  the  selection 
and  breeding  of  medicinal  plants  not  only  promises  to  yield  results 
of  great  practical  importance,  but  also  affords  a  field  for  the  widest 
scientific  activity. 

It  is  to  be  regretted  that  at  present  there  is  no  satisfactory  way 
in  which  the  investigations  being  made  upon  medicinal  plants  in 
different  sections  of  this  country  can  be  properly  correlated  and 
reduced  to  form  for  definite  comparison.  Especially  desirable  is  a 
practical  basis  of  correlation  for  studies  of  the  variation  in  plant 
constituents,  due  in  part,  at  least,  to  differences  in  geographical 
location.  When  two  more  or  less  widely  separated  workers  attempt 
to  compare  the  results  of  their  studies,  it  frequently  happens  that 
they  experience  the  greatest  difficulty  in  harmonizing  their  results. 
This  is  due  in  part  to*  differences  in  the  response  which  plants  make 
when  under  different  environmental  conditions,  in  part,  probably, 
to  variations  in  the  method  of  procedure  followed  in  the  cultivation, 
curing,  and  analysis  of  the  plant,  and  in  part,  no  doubt,  to  differ- 
ences in  the  genetic  relationship  of  the  plants  studied  by  the  respec- 
tive investigators. 

There  seems  to'  be  an  opportunity  for  some  arrangement  or  mutual 
agreement  between  the  representatives  of  our  various  medicinal 
plant  gardens  under  the  terms  of  which  multiplicate  samples  of  seeds 


XveZrerPi9i4m'l  Methods  for  Determination  of  Calomel.  511 

or  plants  of  common  parentage  could  be  distributed  for  the  produc- 
tion of  plants  to  be  used  experimentally.  If  under  such  an  agree- 
ment uniformity  of  treatment  throughout  the  processes  of  culture, 
curing,  and  analysis  could  be  secured,  comparison  of  results  would 
be  much  more  profitable  than  at  present,  and  the  tabulation  and  sum- 
marizing of  the  results  of  experimental  work  conducted  along  the 
lines  indicated  in  a  number  of  localities  would  permit  the  drawing  of 
conclusions  having  a  significance  far  greater  than  those  that  can  be 
reached  by  a  single  isolated  worker.  The  suggestions  here  offered 
contemplate  nothing  like  a  general  cooperative  investigation,  but 
rather  the  adoption  of  what  might  be  regarded  as  a  standard  method 
of  procedure  analogous  to  official  methods  of  analysis,  etc.  The 
tabulation  and  summarizing  of  results  might  well  follow  individual 
publication,  as  no  other  course  is  likely  to  give  satisfaction. 

In  conclusion,  I  wish  to  say  that  the  resources  of  the  experi- 
mental drug  gardens  of  the  Office  of  Drug-Plant  Investigations, 
Bureau  of  Plant  Industry,  are  open  to  any  school  of  pharmacy  desir- 
ous of  starting  a  medicinal  plant  garden,  as  are  also  the  facilities  of 
that  office  for  effecting  the  distribution  of  material  for  experimental 
purposes,  and  for  furthering  the  collection  and  compilation  of  data 
on  the  cultivation  of  medicinal  plants  under  great  diversity  in  con- 
ditions of  growth. 

Bureau  of  Plant  Industry, 
United  States  Department  of  Agriculture, 
August  18,  1914. 


A  STUDY  OF  SOME  OF  THE  METHODS  FOR  THE  DETER- 
MINATION OF  CALOMEL  IN  CALOMEL  TABLETS. 
By  J.  W.  Marden  and  O.  E.  Cushman. 

In  the  determination  of  calomel  in  calomel  tablets  there  is  a 
choice  of  several  methods  of  procedure.  Since  the  composition  of 
calomel  tablets  varies  considerably,  different  methods  apply  better 
to  some  samples  than  to  others,  and  care  must  be  exercised  in  select- 
ing a  method  which  will  give  correct  results  ;  many  fillers,  such  as  talc, 
sodium  bicarbonate,  gum  acacia,  confection  of  rose,  etc.,  are  often 
found. 

Possibly  the  most  widely  used  method  for  the  analysis  of  mer- 
curous  mercury  is  the  gravimetric  estimation  as  the  sulphide.1  In  this 


^Treadwell-Hall,  Anal.  Chem.,  vol.  ii,  p.  168;  Olsen,  Quant.  Chem.  Anal., 
P-  79- 


Si2  Methods  for  Determination  of  Calomel.  4Am-  J(T-  p£Sf?1' 

°  1  J  \   November,  1914. 

method  it  is  necessary  to  oxidize  the  mercury  in  order  to  get  it  into 
solution,  and  for  this  oxidation  strong  acids,  aqua  regia,  free  chlorine, 
or  some  other  suitable  reagents  are  commonly  used.  When  the 
mercury  is  completely  oxidized  the  strong  acids  are  nearly  neutralized 
and  the  clear  solution  treated  with  hydrogen  sulphide.  The  mer- 
curic sulphide  thus  precipitated  always  contains  free  sulphur,  and 
this  must  be  removed  before  the  sulphide  can  be  dried  and  weighed. 
The  precipitate  is  therefore  washed  thoroughly  with  dilute  hydrogen 
sulphide  water  and  finally  washed  repeatedly  with  carbon  disulphide 
to  remove  the  free  sulphur. 

There  are  at  least  three  objectionable  points  in  this  method.  First, 
the  length  of  time  required  for  a  determination  (which  depends,  of 
course,  upon  the  modification  used)  is  much  too  long  for  the  average 
analyst.  Second,  the  difficulty  of  obtaining  complete  oxidation  is 
very  great.  Certain  fillers  seem  to  add  to  this  difficulty,  and  talc, 
if  it  is  present,  remains  suspended  in  the  solution.  In  such  a  case 
there  is  no  way  of  determining  when  the  reaction  is  complete.  The 
use  of  strong  acids  for  the  oxidation  is  inadvisable  because  of  the 
difficulty  in  removing  the  excess  of  acids  before  the  precipitation  of 
the  sulphide,  and,  according  to  Treadwell,  the  nitric  acids  in  the 
aqua  regia,  if  this  is  used,  can  not  be  removed  by  evaporation  be- 
cause of  the  volatility  of  the  mercuric  chloride.  It  was  found  that 
oxidation  with  free  chlorine  in  alkaline  solution  is  the  most  successful, 
as  the  proper  degree  of  acidity  for  complete  precipitation  with 
hydrogen  sulphide  is  more  easily  attainable  here  than  in  the  methods 
employing  concentrated  acids.  Third,  although  a  number  of  modifi- 
cations of  this  method  have  been  suggested  for  the  extraction  of  the 
free  sulphur  with  carbon  disulphide,  none  of  these  have  been  found 
to  give  very  satisfactory  results.  It  is  apparent  that  it  is  very 
difficult  to  wash  out  occluded  sulphur  from  precipitates  unless  they 
are  finely  divided.  Mercuric  sulphide  precipitates,  under  ordinary 
circumstances,  in  clots  which  can  not  be  easily  disintegrated,  and 
considerable  experience  has  shown  that  extraction  with  the  Soxhlet 
apparatus  for  many  hours  does  not  remove  the  sulphur  so  that  the 
results  obtained  could  be  looked  upon  with  confidence. 

According  to  Merrill,2  mercury  can  be  determined  by  the  vola- 
tilization of  the  mercurous  chloride.  In  this  method  the  procedure 
is,  roughly,  to  triturate  the  tablets  in  warm  water  and  transfer  the 


2  E.  C.  Merrill,  Bureau  of  Chemistry,  Washington,  D.  C. 


ANoVf.XiNPih9um' }  Methods  for  Determination  of  Calomel  513 

solid  mercurous  chloride  to  a  Gooch  crucible  which  has  been  pre- 
viously ignited.  The  crucible  and  its  contents  are  washed  thoroughly, 
dried  at  no°  C,  weighed,  ignited  in  a  Bunsen  burner  to  drive  off 
the  mercurous  chloride,  cooled,  and  weighed  again.  The  loss  in 
weight  is  assumed  to  be  mercurous  chloride.  This  method  is  shorter 
and  simpler  than  the  sulphide  method,  but  it  can  not  be  used  for 
the  analysis  of  certain  calomel  tablets.  It  was  found  in  several 
cases  that  fillers  consisted  of  some  ingredients  that  were  insoluble  in 
water  and  various  organic  solvents,  but  were  at  the  same  time 
volatile  or  combustible,  like  cellulose,  thus  giving  a  result  too  high. 

A  method  was  also  tried  for  the  volatilization  of  the  free  mercury 
after  the  calomel  had  been  reduced  with  formaldehyde.  Here  there 
is  no  means  of  telling  when  the  reduction  is  complete,  and  even  after 
considerable  effort  consistent  results  were  not  obtained. 

Merrill  also  suggested  a  method  for  the  reduction  of  mercury 
to  the  metallic  state  with  formaldehyde,  filtering  off  the  free  mercury, 
and  determining  the  chlorine  gravimetrically  as  silver  chloride.  This 
is  open  to  the  same  objections  as  the  preceding  method,  for  com- 
plete reduction  with  formaldehyde  is  somewhat  slow  and  difficult. 

An  iodine  titration  'method  3  is  suggested  by  various  text-books 
on  quantitative  analysis  which  is  rapid  and  gives  good  results  with 
most  samples  of  calomel,  but  very  poor  results  with  a  few  others, 
success  seeming  to  depend  on  the  character  of  the  filler  used.  The 
method  consists  in  treating  the  tablets,  which  have  been  disinte- 
grated with  water,  with  potassium  iodide  and  standard  iodine  solu- 
tion in  excess,  and  titrating  this  excess  with  sodium  thiosulphate 
solution.  A  control  is  run  under  similar  conditions,  and  the  differ- 
ence between  the  amount  of  thiosulphate  solution  used  in  the  control 
and  the  sample  represents  the  iodine  consumed  by  the  calomel.  The 
end  point  in  this  titration  is  not  decisive  and  changes  on  standing. 
It  was  found  in  other  cases  that  the  iodine  did  not  react  as  rapidly 
as  the  method  indicated,  but  that  after  the  iodine  had  been  added  it 
was  better  to*  allow  the  solution  to  stand  before  titration. 

Other  methods  might  be  cited,  but  the  above-mentioned  are  suffi- 
cient to  indicate  the  difficulty  of  devising  a  method  that  is  at  once 
rapid,  accurate,  and  applicable  to  all  cases.  The  need  for  such  a 
method  arose  in  this  laboratory  by  reason  of  the  number  of  samples 


3  Schimpf,  "  Manual  of  Volumetric  Analysis,"  p.  408;  Sutton,  "  Methods  of 
Volumetric»Analysis,"  p.  248. 


5M 


Methods  for  Determination  of  Calomel. 


Am.  Jour.  Pliarm. 
November,  1914. 


of  calomel  received  for  analysis  and  the  limited  amount  of  time 
available.  A  method  was  devised,  which  was  afterward  found  to  be 
identical  with  the  method  recently  suggested  by  Kohn  and  Oster- 
setzer,4  which  seems  to  very  nearly  satisfy  the  conditions.  Kohn 
found  that  the  halogen  compounds  of  mercury  could  be  easily  oxi- 
dized and  made  soluble  by  means  of  sodium  peroxide,  and  the  halogen 
titrated  by  Volhard's  method  with  silver  nitrate.  This  method,  as  it 
has  been  used  for  the  results  below,  is  as  follows :  The  tablets,  in 
amount  corresponding  to  0.2  to  1.0  gm.  of  Calomel,  are  first  disinte- 
grated in  about  30  C.c.  of  water,  made  acid  with  nitric  acid  to  drive 
off  the  carbon  dioxide  from  the  sodium  bicarbonate,  which  is  often 
used  as  a  filler,  and  sodium  peroxide  added,  a  little  at  a  time,  with 
stirring,  until  the  gray  metallic  mercury  separates  out.  About  one 
gramme  of  sodium  peroxide  is  added  in  excess.  After  heating  for 
a  very  few  minutes,  the  precipitated  mercury  is  filtered  onto  a 
Gooch  crucible  and  washed  with  water.  The  filtrate  is  strongly 
acidified  with  nitric  acid,  tenth-normal  silver  nitrate  added  in  excess, 
and  the  solution  then  cooled  and  agitated,  causing  the  precipitate  to 
coagulate.5  The  excess  of  silver  nitrate  is  then  titrated  with  potas- 
sium sulphocyanate,  using  ferric  alum  as  an  indicator.  This  method 
is  rapid,  requiring  only  a  few  minutes  for  a  determination ;  it  is 
simple,  and  it  was  found  to  give  accurate  results  with  all  of  the 
samples  of  calomel  tablets  tried. 

The  first  table  below  gives  a  series  of  results  of  the  analyses  of 
known  amounts  of  pure,  carefully  dried  mercurous  chloride  by 
Kohn's  method,  using  certified  burettes  for  the  titrations. 

The  second  table  gives  the  results  with  mixtures  of  calomel  and 
sodium  carbonate.  This  will  give  an  idea  of  about  how  close  tablets 
consisting  of  these  constituents  could  be  determined  by  this  method. 

Table  I. 


No. 

Gms.  HgCl 

Cc.  N/10  AgN03 

Cc.  N/10  KCNS 

Gms.  HgCl  found 

Per  cent. 

I 

O.50OO 

25.OO 

3-83 

O.4986 

9972 

2 

O.50OO 

25.OO 

378- 

O.4998 

99.98 

3 

O.50OO 

25.OO 

3.83 

O.4986 

9972 

4 

O.50OO 

25.OO 

3.80 

O.4993 

99-86 

5 

O.50OO 

25.OO 

3.83 

O.4986 

99.72 

Average  per  cent 


99.80 


4  Zeits.  anorg.  Chem.,  80,  218. 

6  Rathmund  and  Burgstaller,  Zeits.  anorg.  Chem.,  63,  330  (1909). 


ANoV^XrPi9ir4m' }  Methods  for  Determination  of  Calomel  515 


Table  II. 


1\0. 

Gms.  HgCl 

bms.  JN  a2CU3 

Cc.  N/10 
AgNOs 

Cc.  N/10 
KCNS 

Gms.  HgCl 
found 

Per  cent  found 
in  mixtures 

I 

0.8000 

0.2000 

40.OO 

6.13 

O.7960 

2 

0.8000 

0.2000 

40.OO 

6.12 

O.7968 

7Q  6/1 

3 

0.6000 

O.4OOO 

30.OO 

4.61 

O.5981 

4 

O.60OO 

O.4OOO 

30.00 

4-56 

0-5993 

5 

0.6000 

O.4OOO 

30.00 

4.61 

0.5981 

59-85 

6 

O.40OO 

0.6000 

25.OO 

8.O4 

0.3996 

7 

O.400O 

0.6000 

25.OO 

8.06 

0.3991 

39-94 

8 

0.2000 

0.8000 

15.00 

8.48 

0.1999 

9 

0.2000 

0.8000 

15.OO 

8-43 

0.1985 

19.92 

It  must  be  admitted  that  the  results  obtained  for  this  table  are  a 
little  low,  due  either  to  a  passing  of  the  end  point  in  the  titration,  or 
to  the  reverse  reaction  6  which  occurs  when  the  silver  chloride  is  not 
removed  before  the  excess  of  silver  nitrate  is  titrated. 

The  third  table  shows  some  of  the  results  of  the  analyses  of 
several  samples^  of  calomel  tablets  by  the  sodium  peroxide  method 
and  the  checks  made  by  some  of  the  other  methods  of  analysis.  The 
table  is  condensed,  showing  only  the  average  of  duplicate  determina- 
tions in  each  case.  This  table  is  intended  to  give  an  idea  of  how  the 
amount  of  calomel  found  by  different  methods  varies  with  the  con- 
ditions imposed  by  each  method. 


Table  III. 


No. 

Grains  per 
tablet 
claimed 

Grains  by 
sulphide 
method 

Grains  by 
volume 
of  Hg 

Grains  by 
volume 
of  HgCl 

Grains  by 
iodide 
method 

Grains  by 
Na202 
method 

Per  cent,  of 
labelled 
value 
found  by 
Na20o 
method 

I 

1. 000 

O.992 

I.030 

IO3.O 

2 

1. 000 

0-775 

O.870 

87.O 

3 

0.250 

0.2I2 

O.19O 

O.252 

100.8 

4 

1. 000 

I.OIO 

O.982 

98.2 

5 

1. 000 

I.070 

I.030 

103.0 

6 

0.250 

O.3OO 

O.252 

100.8 

7 

0.500 

0.529  - 

0.525 

105.0 

8 

0.250 

0.333 

0.147 

98.8 

9 

0.250 

O.208 

O.260 

O.204 

81.6 

10 

0.250 

O.230 

O.239 

O.258 

103.2 

11 

0.500 

0-459 

0-494 

98.8 

12 

1. 000 

I.O95 

O.946 

94.6 

Average   97.9 


"Rosanoff  and  Hill,  /.  Am.  Chem.  Soc,  29,  269  (1907). 


516  Is  the  Present  an  Opportune  Timet     ^XvlXr™  T' 

It  will  be  noted  that  the  results  by  the  sulphide  method  are  some- 
what low,  due  probably  to  incomplete  oxidation  of  the  calomel. 
The  results  by  the  reduction  to  metallic  mercury  and  subsequent 
volatilization  are  variable,  and  by  volatilization  without  reduction 
they  are  high,  as  might  be  expected.  The  last  column  of  Table  III 
may  also  be  used  to  show  how  close  the  calomel  tablets  put  out  by 
good  firms  check  their  labelled  values.  No.  9  illustrates  a  case  where 
oil  is  used  in  compounding  the  tablets,  and  the  high  result  by  the 
iodide  method  indicates  a  possible  absorption  of  iodine  by  the  oil 
present.  ;    ,  I 

In  conclusion  it  is  important  to  note  that  no  case  has  as  yet  been 
encountered  where  the  sodium  peroxide  titration  method  did  not  give- 
consistent  results,  and  no  trouble  was  found  due  to  imperfect  oxi- 
dation. Undoubtedly  much  of  the  discrepancy  in  results  is  due  to 
the  chipped  condition  in  which  the  tablets  were  found,  in  some  cases 
it  being  difficult  to  obtain  the  proper  number  of  unbroken  tablets. 
In  several  cases  the  tablets  were  weighed  and  the  calomel  then 
figured  on  a  percentage  basis,  thus  checking  the  consistency  of  the 
work  of  the  operator.  In  unbroken  tablets  a  variation  of  several 
per  cent,  in  their  weights  was  found,  which  would  explain  much  of 
the  variation  in  the  last  column  of  Table  III.  Briggs  7  considers 
that  15  per  cent,  variation  in  weight  would  not  be  excessive,  which 
seems,  however,  to  be  larger  than  is  necessary. 

The  South  Dakota  Food  and  Drug  Department,  Vermilion. 


IS  THE  PRESENT  AN  OPPORTUNE  TIME  FOR  THE  RE- 
VISION OF  OUR  PATENT  LAWS  IN  SO  FAR  AS  THEY 
AFFECT   MEDICINAL  AND   CHEMICAL  PRODUCTS? 

By  John  K.  Thum,  Pharmacist  at  the  German  Hospital,  Philadelphia. 

At  the  October  meeting  of  the  Philadelphia  Branch  of  the  Ameri- 
can Pharmaceutical  Association  there  was  more  or  less  discussion 
as  to  the  advisability  of  urging  upon  Congress  at  this  time  the  need 
of  an  equitable  revision  of  our  Patent  Laws  in  so  far  as  they  relate 
to  medicines  and  chemicals  for  the  use  of  the  sick. 

There  is  no  need  at  this  time  to  enter  into  details  as  to  the  neces- 
sity for  such  revision.   All  well-informed  pharmacists  are  aware  of 


7  Briggs,  J.  Am.  Phar.  Assoc.,  vol.  iii,  33  (1914). 


YoVeJ£r,wT' }        Digitalis  and  Its  Preparations.  5 1 7 

the  fact  that  foreign  manufacturers  have  enjoyed  a  rich  harvest  for 
years,  and  waxed  rich  at  our  expense  by  taking  advantage  of  these 
laws  which  give  a  patent  on  a  medicinal  or  chemical  product. 

Dr.  F.  E.  Stewart,  who  is  chairman  of  the  Committee  on  Patents 
and  Trade  Marks  of  the  American  Pharmaceutical  Association,  and 
who*  is  recognized  as  an  authority  on  such  matters,  was  present  at 
this  meeting  and  in,  the  course  of  the  discussion  mentioned  that  the 
last  time  he  was  at  Washington  advocating  legislation  along  these 
lines  a  United  States  Senator  said  "  that  so  long  as  the  different 
organizations  and  branches  of  the  drug  trade  came  before  Congress, 
each  with  different  ideas  and  plans,  it  would  be  impossible  for 
Congress  to  do  anything.  You  must  get  together  and  agree  as  to 
what  you  want  and  then  we  can  help  you." 

If  all  the  different  interests  of  the  drug  trade  in  this  country 
were  able  to  get  together  on  the  "  Harrison  Anti-Narcotic  Bill,"  why 
should  they  not  be  able  to  get  together  on  a  matter  which  has 
for  its  object  a  just  and  equitable  revision  of  our  Patent  Law 
as  it  affects  our  calling?  Why  not  put  this  matter  up  to  the  Na- 
tional Drug  Trade  Conference,  and  have  this  body  debate  the 
matter  thoroughly  and  formulate  some  definite  plan  that  will  be 
fair  and  just  to  the  consumers  of  medicinal  products  in  this  country, 
to  those  who  are  responsible  for  them  and  to  those  various  interests 
of  our  calling  who1  must  handle  and  distribute  them? 

Now  is  the  time  to  push  forward  this  great  work.  For  years 
and  years  this  question  has  been  under  more  or  less  discussion. 
One  could  hardly  attend  a  meeting  of  either  a  State  or  National 
Association  without  hearing  something  said  about  it.  Its  importance 
and  necessity  is  conceded  by  everyone,  so  why  not  have  the  various 
interests  act  in  concert  ?  Never  has  American  pharmacy  had  a  more 
favorable  and  opportune  time  for  the  furthering  and  carrying  out 
of  a  truly  great  piece  of  constructive  legislation. 


DIGITALIS  AND  ITS  PREPARATIONS. 

It  is  particularly  encouraging  to  those  who  advocate  a  more 
rational  study  and  intelligent  administration  of  drugs,  especially  in 
these  days  when  the  medical  profession  is  being  bombarded  on  all 
sides  with  so-called  newer  preparations  of  digitalis,  to  know  that 
the  result  of  practical  research  work  done  by  men  who  have  no  axes 
to  grind  is  available  to  help  along  such  a  propaganda. 


5 1 8  Digitalis  and  Its  Preparations.        \  kfJ^J\^ 


In  a  paper  entitled  "  Digitalis  and  Its  Preparations,"  and  which 
might  well  be  called  "  The  Truth  About  Digitalis,"  Dr.  Robert  A. 
Hatcher,  professor  of  pharmacology  at  Cornell  University,  explodes 
some  conceptions  of  this  drug. 

Digitalis,  Dr.  Hatcher  states,  acquired  a  reputation  as  a  house- 
hold remedy  in  dropsy  some  time  before  jt  was  introduced  into 
medical  literature.  One  of  the  earliest  of  writers  about  this  drug 
was  Dr.  Withering,  an  English  physician.  This  physician  stated  that 
the  wild-grown  drug  was  more  active  than  the  cultivated.  This 
belief,  Dr.  Hatcher  says,  continues  to  be  still  accepted.  It  is  also 
believed  that  only  the  leaves  of  the  second  year's  growth  collected 
at  the  time  of  flowering  should  be  used.  This  claim  is  supported  by 
most  of  the  pharmacopoeias  of  the  world.  How  this  belief  originated 
no  one  knows,  but  it  surely  was  the  result  of  superficial  observations, 
as  Worth  Hale  and  other  pharmacologists  have  found,  through 
experiments  on  animals,  that  leaves  of  the  first  year  are  more  active 
than  the  average  leaf  of  the  second  year.  And  it  is  very  interesting 
to  know  that  the  leaves  used  in  this  work  were  from  cultivated  plants. 

"  Another  curious  misconception  regarding  digitalis  which  is 
hard  to  explain  is  that  the  leaf  grown  in  certain  regions  is  more 
active  than  that  grown  in  other  localities.  It  has  often  been  stated 
that  the  Bohemian  leaf  is  too  toxic  for  therapeutic  use.  Leaves 
grown  in  a  single  locality  often  show  great  variations  in  activity, 
and  it  is  true  that  Bohemian  digitalis  is  often  very  potent.  The 
toxic  action  of  digitalis  is  simply  an  extension  of  the  therapeutic 
action,  and  it  would  be  as  logical  to  complain  of  the  toxicity  of 
aconite  or  mix  vomica  as  of  that  of  digitalis. 

4<  At  the  other  extreme  is  the  view  that  activity  and  quality  must 
necessarily  run  parallel.  Other  things  being  equal,  a  drug  of  a  given 
degree  of  activity  is  preferable  to  one  showing  but  half  of  the  activ- 
ity ;  but  the  case  with  digitalis  is  not  quite  so  simple,  and  it  is  far  more 
important  to  have  a  drug  of  uniform  activity  than  to  have  the  most 
active  drug  that  can  be  obtained.  Furthermore,  even  a  uniformly 
potent  digitalis  is  not  necessarily  better  than  a  uniform  one  of  less 
potency,  for  digitalis  contains  (or  yields)  several  therapeutic  prin- 
ciples, and  at  least  one  substance,  saponin,  which  is  of  minor  toxico- 
logical  importance  ; — of  minor  importance  because  it  is  present  in  the 
leaf  only  in  traces.  While  all  of  the  therapeutic  principles  of  digitalis 
exert  a  more  or  less  qualitatively  similar  action  on  the  heart,  they 
differ  in  certain  essential  side  actions,  and  it  does  not  necessarily 


Am.  Jour.  Pharm.  ) 
November,  1914.  J 


Digitalis  and  Its  Preparations. 


519 


follow  that  the  most  active  specimen  of  digitalis  contains  the  largest 
proportion  of  the  most  desirable  of  these  principles.  Thus,  true  digi- 
talin  (of  Schmiedeberg)  is  more  actively  emetic  than  digitoxin  in 
proportion  to  its  therapeutic  activity  (contrary  to  common  teaching), 
and  it  may  be  that  one  specimen  which  is  more  active  than  another 
may  contain  the  larger  proportion  of  this  relatively  more  active 
emetic,  true  digitalin,  in  which  case  the  less  active  drug  would  be 
decidedly  the  more  valuable. 

"  We  need  digitalis  which  will  exert  a  maximum  therapeutic 
action  with  a  minimum  of  this  undesired  action,  regardless  of  whether 
the  drug  is  from  wild  or  cultivated  plants,  and  whether  of  the  first 
or  second  year's  growth,  and  regardless  of  the  actual  activity,  even 
within  certain  limits,  for  one  may  administer  a  larger  or  smaller 
dose,  provided  the  activity  of  the  drug  be  known." 

The  study  of  digitalis  from  this  point  of  view  has  received  little 
or  no  attention,  and  Dr.  Hatcher  states  that  it  is  a  field  to  which 
the  pharmacist  could  well  give  some  attention.  The  disagreeable 
features  of  this  drug  is  its  tendency  toward  nausea  and  vomiting, 
and  while,  to  a  certain  extent,  this  is  unavoidable,  there  is  a  possi- 
bility of  minimizing  it  if  one  can  only  find  out  at  what  season  the 
drug  shows  a  minimum  emetic  action  relative  to  its  therapeutic  effect. 

While  digitalis,  like  other  vegetable  drugs,  will  deteriorate  when 
improperly  stored,  the  extraordinary  precautions  and  requirements 
of  some  of  the  European  pharmacopoeias  are  unnecessary ;  specimens 
of  the  whole  or  powdered  leaves  examined  in  the  laboratory  showed 
no  evidence  of  deterioration  after  having  been  stored  in  the  most 
ordinary  manner  in  paper  boxes,  during  periods  varying  from  five 
to  twenty-five  years. 

Speaking  on  the  subject  of  digitalis  from  a  pharmaceutical  stand- 
point, this  investigator  emphasizes  the  necessity  of  a  proper  alcoholic 
content  in  its  liquid  preparations.  Tinctures  and  fluidextracts  should 
not  only  be  made  with  a  menstruum  of  70  per  cent,  alcohol,  but  the 
finished  preparation  should  actually  contain  that  amount  of  alcohol ; 
when  this  requirement  is  complied  with  deterioration  does  not  take 
place  in  any  important  degree.  Digitalis  leaf  and  the  preparations 
containing  this  amount  of  alcohol  will  retain  their  potency  almost 
indefinitely  without  any  serious  loss  if  protected  from  air  and 
sunlight. 

Physicians  who  are  inclined  to  be  susceptible  to  the  wiles  of  the 
detail  man  would  do  well  to  ponder  these  words:  "Unfortunately, 


520  Philadelphia  College  of  Pharmacy.  {^oveSrfmT' 

with  the  appearance  of  every  proprietary  preparation  bearing  a  new 
label  and  accompanied  by  the  usual  clinical  support  of  its  pretensions 
physicians  run  after  it  for  a  time,  believing  that  the  mystery  of 
digitalis  has  been  solved  at  last.  The  more  observant  usually  return 
£b  the  use  of  a  good  tincture,  or  the  powdered  leaf,  when  that  is 
obtainable,  and  the  wise  pharmacist  will  stand  ever  ready  to  supply 
a  dependable  leaf,  and  a  standardized  tincture  of  his  own  manu- 
facture." 

It  is  generally  believed  that  there  is  a  difference  in  action  between 
the  infusion  and  tincture  of  this  drug,  but  such  is  not  the  case;  the 
tincture  supposedly  acting  more -on  the  heart  and  the  infusion  as  a 
diuretic.  Dr.  Hatcher  shows  very  clearly  that  a  properly  made  in- 
fusion and  tincture  contains  all  of  the  therapeutically  active  prin- 
ciples of  digitalis.  The  investigator  also  says  it  is  easy  to  demonstrate 
that  the  marc  left  after  preparing  the  tincture  is  inert  by  simply  pre- 
paring an  infusion  from  this  marc  and  testing  on  a  frog.  The  result 
is  negative. — The  Druggists'  Circular,  Sept.,  1914,  page  517. 

J.K.T. 


PHILADELPHIA  COLLEGE  OF  PHARMACY. 

Semi-annual  Meeting. 

The  semi-annual  meeting  of  the  Philadelphia  College  of  Phar- 
macy was  held  September  28,  1914,  at  4  p.m.,  in  the  Library,  the 
President,  Howard  B.  French,  presiding.  Twenty-one  members 
were  present. 

The  minutes  of  the  quarterly  meeting  held  June  29th  were  read 
and  approved. 

The  minutes  of  the  Board  of  Trustees  for  the  meetings  held 
June  2d  and  9th  and  July  12th  were  read  by  the  Registrar  and 
approved. 

The  Committee  on  nominations  presented  the  list  of  names  for 
vacancies  in  the  Board  of  Trustees.  The  report  was  ordered  entered 
and  filed.  The  Committee  on  Membership  reported  for  the  year, 
making  suggestions  to  increase  the  membership.  The  President 
announced  the  death  of  the  following  members  since  the  last  meet- 
ing :  George  J.  Scattergood,  William  E.  Lee,  and  Henry  C.  Eddy. 

The  President  appointed  as  tellers  to  conduct  the  election  for 
Trustees,  Dr.  Mitchell  Bernstein  and  E.  H.  Hessler. 


November Si™"}     Philadelphia  College  of  Pharmacy.  521 

While  the  tellers  were  counting  the  ballots  Professor  Remington 
reported  verbally  for  the  delegates  to  the  American  Pharmaceutical 
Association  meeting  recently  held  at  Detroit,  Michigan.  A  full 
report  of  the  meeting  by  M.  I.  Wilbert  was  published  in  the  Ameri- 
can Journal  of  Pharmacy,  September  number,  pages  464  to  471. 

The  tellers  reported  the  results  of  the  ballot  for  Trustees,  that 
George  M.  Beringer,  Joseph  W.  England,  and  C.  Mahlon  Kline  had 
been  elected  for  three  years,  and  Samuel  C.  Henry  for  one  year, 
whereupon  the  President  declared  the  gentlemen  named  as  duly 
elected. 

The  President  appointed  the  Committee  on  Membership  as  fol- 
lows :  Charles  H.  La  Wall,  O.  W.  Osterlund,  Richard  H.  Lackey, 
with  the  Treasurer  and  Secretary  ex-ofdcio. 

Mr.  Jacob  S.  Beetem  reported  that  Mr.  Frederick  Gutekunst, 
a  graduate  of  the  College,  had  reached  the  age  of  eighty- three  years, 
and  he  would  suggest  that  the  congratulations  of  the  College  be 
tendered  Mr.  Gutekunst.  The  suggestion  was  approved  and  the 
President  appointed  Professor  La  Wall  to  prepare  a  suitable  minute, 
when  the  following  was  presented  and  unanimously  adopted :  "  We, 
the  members  of  the  Philadelphia  College  of  Pharmacy  in  semi-annual 
meeting  assembled,  do  hereby  extend  the  congratulations  of  the 
College  to  Mr.  Frederick  Gutekunst  upon  having  successfully 
reached  his  eighty-third  birthday.  We  are  proud  to  feel  that  the 
great  measure  of  his  success  has  been  partly  due  at  least  to  the 
training  which  he  received  many  years  ago  in  our  institution,  and 
we  hope  that  he  may  be  spared  to  add  many  more  laurels  to  his 
wreath  of  achievements." 

It  was  also  voted  that  the  thanks  of  the  College*  be  tendered  Mr. 
Gutekunst  for  the  donation  of  photographs  of  some  of  the  present 
and  past  officers  and  faculty  of  the  College. 

It  was  also  voted  that  the  thanks  of  the  College  be  tendered  Mr. 
George  B.  Evans  for  the  gift  of  a  number  of  bronze  mortars  and 
pestles  and  several  other  ornaments  of  value,  collected  by  him  in 
Europe. 

C.  A.  Weidemann,  M.D., 

Recording  Secretary. 


522  Minutes  of  Board  of  Trustees.        { AJv^ ™g™ 1 


ABSTRACTS  FROM  THE  MINUTES  OF  THE 
BOARD  OF  TRUSTEES. 

June  2nd,  1914. — Sixteen  members  present.  Committee  on  an- 
nouncement reported  the  catalogue  number  of  the  Bulletin  in  press. 
A  sketch  of  the  new  certificate  was  adopted,  and  the  Registrar  was 
directed  to  place  an  order  at  the  price  agreed  upon.  Mr.  Campbell, 
for  the  Special  Committee  on  N.  A.  R.  D.  exhibit,  reported  having 
arranged  for  a  booth  at  their  Convention,  and  explained  the  nature 
of  the  exhibit.  Mr.  George  B.  Evans  kindly  agreed  to  assist  in 
making  the  exhibit  attractive,  and  also  recommended  that  the  ex- 
hibit be  made. 

June  pth,  19 1 4. — Adjourned  meeting.  Sixteen  members  present. 
Committee  on  Examinations  presented  the  names  of  those  recom- 
mended for  the  degree  of  Doctor  in  Pharmacy  (P.D.).  A  teller  was 
appointed  and  the  ballot  was  then  taken  and  reported  clear,  and  the 
Chair  then  declared  those  named  elected  to  receive  the  degree  of 
Doctor  in  Pharmacy.  The  names  of  those  recommended  for  the 
degree  of  Pharmaceutical  Chemist  (P.C.)  was  then  read,  and,  a 
ballot  being  taken  and  reported  clear,  the  Chair  declared  them 
elected  to  receive  the  degree  of  Pharmaceutical  Chemist.  The  com- 
mittee reported  that  Professors  Sadtler  and  Moerk  had  recom- 
mended that  a  Certificate  of  Proficiency  in  Chemistry  be  awarded 
to  Harry  C.  Karns,  P.D.  The  recommendation  was  approved.  The 
committee  also  presented  a  communication  from  Professor  Roddy 
giving  the  names  of  those  entitled  to  receive  a  Certificate  in  Bacteri- 
ology, and  recommended  that  they  be  granted.  It  was  so  ordered. 
The  committee  also  presented  the  name  of  Paul  Donmoyer,  Class  oi 
1907,  for  a  Certificate  in  Bacteriology,  as  recommended  by  Professor 
Kraemer.  On  motion  it  was  ordered  that  the  certificate  be  granted 
and  that  others  who  had  taken  the  course  under  Professor  Kraemer 
and  had  passed  the  required  examination  should  be  granted  certifi- 
cates and  Professor  Kraemer  be  authorized  to  sign  same.  The 
names  of  those  who  had  won  prizes  were  then  read,  and  the  Chair 
appointed  those  who  were  to  present  same  at  the  Commencement 
exercises.  Committee  on  Commencement  reported  that  Governor 
Tener  had  consented  to  address  the  Graduating  Class.  Mr.  Rumsey 
moved  that  a  vote  of  thanks  be  conveyed  to  those  assisting  in  the 
Commencement  exercises.    It  was  so  ordered. 


ANovoXeVPih9ai4m'}    Objectionable  Labelling  of  Medicines.  523 

July  22nd,  1914. — A  special  meeting  of  the  Board  was  held,  in 
answer  to  the  call  of  three  members,  to  take  action  on  the  death  qf 
William  E.  Lee,  a  member  of  the  Board.  Eleven  members  were 
present,  and  regrets  at  not  being  able  to  be  present  were  receiyed 
from  seven  members.  Remarks  appropriate  to  the  life  and  char- 
acter of  Mr.  Lee  were  made  by  Messrs.  Boring,  Campbell,  England, 
Moerk,  Poley,  and  Weidemann.  Mr.  Mulford  moved  that  a  com- 
mittee of  three  be  appointed  to  draft  resolutions  to  be  entered  on 
the  minutes  and  an  engrossed  copy  sent  to  the  family.  Being  so 
ordered,  the  Chair  appointed  Messrs.  Mulford,  England,  and  Camp- 
bell as  the  committee.  It  was  suggested  that  flowers  be  sent  to  the 
house  on  the  day  of  the  funeral.  This  being  considered  a  special 
tribute,  the  members  personally  paid  the  expense. 


DEPARTMENT  OF  AGRICULTURE  DISCUSSES  OBJEC- 
TIONABLE LABELLING  FOR  MEDICINAL 
PREPARATIONS. 

In  answer  to  many  inquiries  as  to  proper  labelling  for  medicinal 
preparations  to  comply  with  the  Food  and  Drugs  Act  as  amended, 
the  Department  of  Agriculture,  through  the  Bureau  of  Chemistry, 
has  issued  the  following  suggestions  to  makers  and  proprietors  of 
medicinal  preparations : 

1.  Claims  of  Therapeutic  Effects. — A  preparation  cannot  be  prop- 
erly designated  as  a  specific,  cure,  remedy,  or  recommended  as  in- 
fallible, sure,  certain,  reliable  or  invaluable,  or  bear  other  promises 
of  benefit,  unless  the  product  can,  as  a  matter  of  fact,  be  depended 
upon  to  produce  the  results  claimed  for  i  Before  making  any 
such  claim  the  responsible  party  should  care  "uliy  consider  whether 
the  proposed  representations  are  strictly  in  harmony  with  the  facts ; 
in  other  words,  whether  the  medicine,  in  the  light  of  its  composition, 
is  actually  capable  of  fulfilling  the  promises  made  for  it.  For  in- 
stance, if  the  broad  representation  that  the  product  is  a  remedy  for 
certain  diseases  is  made,  as,  for  example,  by  the  use  of  the  word 
"  remedy  "  in  the  name  of  the  preparation,  the  article  should  actually 
be  a  remedy  for  the  affections  named  upon  the  label  under  all  condi- 
tions, irrespective  of  kind  and  cause. 

2.  Indirect  Statements. — Not  only  are  direct  statements  and  rep- 


524  Objectionable  Labelling  of  Medicines.  {'A£oviS«*wi?: 

reservations  of  a  misleading  character  objectionable,  but  any  sugges- 
tion, hint,  or  insinuation,  direct  or  indirect,  or  design  or  device  that 
may  tend  to  convey  a  misleading  impression,  should  be  avoided. 
This  applies,  for  example,  to  such  statements  as  "  has  been  widely 
recommended  for,"  followed  by  unwarranted  therapeutic  claims. 

3.  Indefinite  and  Sweeping  Terms. — Representations  that  are  un- 
warranted on  account  of  indefiniteness  of  a  general  sweeping  char- 
acter should  be  avoided.  For  example,  the  statement  that  a  prepara- 
tion is  "  for  kidney  troubles  "  conveys  the  impression  that  the 
product  is  useful  in  the  treatment  of  kidney  affections  generally. 
Such  a  representation  is  misleading  and  deceptive  unless  the  medi- 
cine in  question  is  actually  useful  in  all  of  these  affections.  For  this 
reason  it  is  usually  best  to  avoid  terms  covering  a  number  of  ail- 
ments, such  as  "  skin  diseases,  kidney,  liver,  and  bladder  affections," 
etc.  Rheumatism,  dyspepsia,  eczema,  and  the  names  of  many  other 
affections  are  more  or  less  comprehensive,  and  their  use  under  some 
circumstances  would  be  objectionable.  For  example,  a  medicine 
should  not  be  recommended  for  rheumatism  unless  it  is  capable  of 
fulfilling  the  claims  and  representations  made  for  it  in  all  kinds  of 
rheumatism.  To  represent  that  a  medicine  is  useful  for  rheumatism, 
when  as  a  matter  of  fact  it  is  useful  in  only  one  form  of  rheumatism, 
would  be  misleading,  such  statements  as  "  for  some  diseases  of  the 
kidney  and  liver,"  "  for  many  forms  of  rheumatism,"  are  objection- 
able, on  account  of  indefiniteness. 

Names  like  "heart  remedy,"  "kidney  pills,"  "  blood  purifier," 
"  nerve  tonic,"  "  bone  liniment,"  "  lung  balm,"  and  other  terms 
involving  the  names  of  parts  of  the  body  are  objectionable  for 
similar  reasons. 

4.  Testimonials. — Testimonials,  aside  from  the  personal  aspect 
given  them  by  their  letter  form,  hold  out  a  general  representation  to 
the  public  for  which  the  party  doing  the  labelling  is  held  to  be  re- 
sponsible. The  fact  that  a  testimonial  is  genuine  and  honestly 
represents  the  opinion  of  the  person  writing  it  does  not  justify  its 
use  if  it  creates  a  misleading  impression  with  regard  to  the  results 
which  the  medicine  will  produce. 

No  statement  relative  to  the  therapeutic  effects  of  medicinal 
products  should  be  made  in  the  form  of  a  "  testimonial  "  which 
would  be  regarded  as  unwarranted  if  made  as  a  direct  statement  of 
the  manufacturer. 


ANoVeJmbeV^h9um'  \     Goldenseal  an  Admirable  Side  Crop.  525 


5.  Refund  Guarantee.— Statements  on  the  labels  of  drugs  guar- 
anteeing them  to  cure  certain  diseases  or  money  refunded  may  be 
so  worded  as  to  be  false  and  fraudulent  and  to  constitute  misbranding. 
Misrepresentations  of  this  kind  are  not  justified  by  the  fact  that  the 
purchase  price  of  the  article  is  actually  refunded  as  promised. 

Washington,  D.  C. 


GINSENG  GROWERS  MAY  FIND  GOLDENSEAL  AN 
ADMIRABLE  SIDE  CROP. 

However,  Market  for  this  Native  Drug  Plant  is  Limited,  Labor  Costs 
are  High,  and  Special  Care  in  Cultivation  is  Necessary. 

Goldenseal  is  a  native  drug  plant  of  admitted  commercial  value, 
which  is  rapidly  becoming  scarce,  and  farmers  who  have  had  experi- 
ence with  ginseng  may  find  in  goldenseal  an  admirable  side  or  suc- 
cession crop.  This  is  the  opinion  of  one  of  the  U.  S.  Department 
of  Agriculture's  drug-plant  specialists,  whose  pamphlet,  "Golden- 
seal Under  Cultivation,"  has  just  been  issued  as  Farmers'  Bulletin 
613.  Goldenseal,  known  to  the  pharmacist  and  physician  as  Hydras- 
tis, is  native  to  open  woodland  where  there  is  ample  shade,  good 
natural  drainage,  and  an  abundance  of  leaf  mold.  It  is  most 
abundantly  found  in  Ohio,  Indiana,  West  Virginia,  and  Kentucky, 
though  it  grows  west  to  Minnesota,  south  to  Georgia,  and  in  southern 
New  York.  It  is  not  grown  in  Europe  on  a  commercial  scale,  and 
the  United  States  exports  quantities  of  this  drug  to  Germany. 

In  general,  drug  plants  are  difficult  to  grow,  labor  costs  are  high, 
and  the  market  is  limited.  These  drawbacks  are  true  to  goldenseal 
but  ginseng  growers  who  are  already  equipped  for  the  culture  of 
exacting  woodland  plants,  but  whose  ginseng  crops  have  been 
attacked  by  pests  and  diseases,  should  meet  with  some  success  with 
goldenseal.  The  latter  requires  essentially  the  same  conditions  as 
the  other  crop,  but  is  easier  to  grow,  being  far  less  subject  to  dis- 
ease and  attacks  from  mice. 

Steady  Advance  in  Market  Price. 

There  began  to  be  a  commercial  demand  for  goldenseal  about 
i860,  and  since  then  its  use  has  become  world-wide,  although  most 
of  it  is  consumed  in  this  country.    It  is  valued  solely  for  its  remedial 


526  Goldenseal  an  Admirable  Side  Crop.  |Aj 


m.  Jour.  Pharm. 
November,  1914. 


properties,  and  was  commonly  used  by  Indians  and  early  settlers 
as  a  remedy  for  sore  mouth  and  inflamed  eyes ;  also  as  a  bitter  tonic 
in  stomach  and  liver  troubles. 

Until  about  the  year  1880  the  prices  paid  for  crude  goldenseal 
rarely  ranged  over  8  to  12  cents  a  pound,  these  prices,  as  a  matter 
of  course,  being  based  on  the  actual  cost  of  collecting  and  curing  the 
material  where  it  was  abundant.  In  1890,  however,  the  approaching 
scarcity  of  the  root  was  manifested  by  rising  prices,  and  at  the  close 
of  the  next  decade  the  cost  had  advanced  to  an  average  of  58  cents 
a  pound.  Early  in  1904  the  price  passed  the  dollar  mark,  the  year 
closing  with  wholesale  quotations  varying  from  $1.35  to  $1.50. 

With  the  exception  of  slight  fluctuations  in  1912,  which  were 
apparently  the  result  of  overcollection,  there  has  been  a  steady 
advance  in  the  price  of  the  dried  root,  both  wild  and  cultivated. 
The  prices  paid  to  growers  and  collectors  of  goldenseal  for  the  last 
three  years  have  ranged  from  $3  to  $4.25  a  pound,  and  these  prices 
are  thought  to  be  a  fair  basis  of  profit  in  goldenseal  culture, 
even  after  taking  into  consideration  the  rather  exacting  requirements 
of  the  plant  and  its  relatively  slow  progress  toward  commercial! 
maturity. 

Not  an  Easy  Crop  to  Grow. 
It  costs  about  $1500  an  acre,  exclusive  of  the  value  of  the 
land,  to  start  a  goldenseal  plantation.  This  includes  the  average 
cost  for  propagating  material,  but  makes  no  provision  for  irrigation 
during  dry  weather.  Of  course,  special  conditions,  such  as  local 
cost  of  labor,  lumber,  and  fertilizers',  will  influence  this  estimate. 
This  outlay  might  well  discourage  those  who  wish  to  cultivate  the 
plant  on  a  large  scale,  but  small  home  and  experimental  plantings 
may  usually  be  started  at  a  very  small  cost.  In  any  case  the  plan 
requires  special  care  and  suitable  conditions  at  all  stages  of  its 
development. 

Goldenseal  takes  considerable  time  to  develop.  If  it  is  grown 
from  seed  under  favorable  conditions  it  only  reaches  its  best  develop- 
ment for  market  after  about  five  years.  If  it  is  grown  from  root 
buds  or  by  division  of  the  rootstock,  it  reaches  its  best  development 
in  three  or  four  years.  Successful  growers  have  outputs  of  about 
2000  pounds  of  dried  root  per  acre  after  five  years  from  seed. 
Better  showings  might  be  made  by  well-equipped  small  growers. 


ANoVSreVPiia/™'}  Poisonous  Nature  of  Jatropha  Urens.  527 

A  market  for  goldenseal  is  found  with  the  crude  drug  dealers 
and  manufacturing  druggists  in  most  large  cities.  This  root  is  also 
handled  on  commission  and  is  readily  purchased  by  fur  buyers  and 
traders  in  miscellaneous  forest  products.  The  estimated  annual 
consumption,  however,  is  only  100  tons,  and  as  only  about  500  acres 
would  be  needed  to  produce  that  amount,  overproduction  would  be 
easy.  Prospective  planters  must  bear  this  in  mind,  as  well  as  the 
fact  that  this  estimate  makes  no  allowance  for  the  wild  supply  of  the 
root,  which  is  still  a  factor,  although  rapidly  decreasing. 

Ginseng  growers  will  be  interested  in  the  new  bulletin  on  golden- 
seal. It  goes  into  great  detail  regarding  methods  of  cultivation,  and 
may  be  had  free  on  application  to  the  Division  of  Publications, 
U.  S.  Department  of  Agriculture,  Washington,  D.  C. 


THE  POISONOUS  NATURE  OF  THE  STINGING  HAIRS 
OF  JATROPHA  URENS1 

Jatropha  urens  is  one  of  the  most  abundant  Euphorbiaceous  plants 
growing  in  or  around  the  savannas  of  the  Pacific  coast  of  Central 
America.  Its  spread  is  favored  by  the  fact  that  the  cattle  avoid  it, 
and  because  it  is  not  kept  down  by  the  too  indolent  owners  of  the 
pastures.  Everywhere  it  has  the  reputation  of  being  extremely 
dangerous,  on  account  of  its  poisonous  effects. 

The  plant  is  easily  recognized:  It  is  herbaceous,  0.5  to  1.5  meter 
high,  regularly  ramified,  with  large,  palmatilobate  leaves,  white 
flowers  and  small,  3-celled  capsules.  All  parts,  trunk,  leaves,  flowers 
and  fruits  are  covered  with  long,  hard  and  glossy,  stinging  hairs, 
which  protect  the  plant  as  barbed  wire  protects  the  fortifications  of 
to-day.  It  would  seem  as  if  the  remarkable  glossiness  of  the  stinging 
hairs  might  warn  the  curious  against  approaching  or  touching.  As 
a  matter  of  fact,  the  animals,  either  by  instinct  or  on  account  of  the 
wisdom  acquired  through  some  previous  experience,  avoid  contact 
with  it. 

The  vernacular  name  of  Jatropha  urens  is  "  ortiga  "  or  "  ortiga 
brava  "  (nettle)  in  Panama,  and  other  parts  of  Central  America, 
indicating  somewhat  its  noxious  effects.  Sometimes  it  is  also  called 
"  chichicaste." 


1  Science,  October  23,  1914,  p.  609. 


528  Poisonous  Nature  of  Jatropha  Urens.  {^viS/mF' 

The  stinging  hairs  of  Jatropha  urens  show  the  same  structure 
as  those  of  the  common  nettle  ( Urticacese ) ,  though  the  two  plants 
belong  to  different  families.  The  poison  is  produced  by  a  cell  of  the 
epidermis  which,  during  the  growth,  swells  up,  forming  a  goblet- 
shaped  bulb,  set  into  the  surrounding  tissue.  The  hair  then  represents 
a  long  tube,  the  walls  of  which  have  incrustations  of  silicic  acid  in 
the  upper  part  and  are  calcified  in  the  lower  parts,  so  that  they  are 
very  brittle  and  break  at  the  lightest  touch.  Near  the  top  this  cell 
expands  a  little,  in  the  form  of  a  miniature  hat  with  very  thin  walls, 
so  that  when  touched,  it  breaks  in  an  oblique  direction,  forming  the 
point  of  a  cannula,  which  enters  the  skin  of  animal  or  man.  At  the 
same  time  the  poisonous  liquid  of  the  cell  is  discharged  into  the 
wound,  and  produces  instantly  a  local  inflammation.  The  mechan- 
ism is,  in  fact,  the  same  as  that  of  the  poison  fang  of  the  snakes,  and 
it  is  also  similar  to  the  cannula  of  the  surgeon. 

To  estimate  the  formidable  effects  of  the  hair  and  the  intensity 
of  its  poisonous  liquids,  it  has  been  calculated  that  about  10,000  hairs 
of  the  common  nettle  may  produce  one  drop  of  poison  (0.05  c.cm.). 
As  in  the  case  I  am  going  to  mention,  about  10  hairs  of  the  Jatropha 
were  broken.  It  may  be  calculated  on  the  same  basis  that  about 
0.00005  c.cm.  of  poison  entered  the  wound.  This  is,  however,  a  low 
estimate,  because  the  hairs  of  our  plant  and  their  inner  cavity  are 
larger  than  those  of  the  common  nettle  and  the  amount  of  poison 
introduced  into  the  system  in  the  following  occurrence  was  prob- 
ably much  larger  than  it  would  have  been  in  the  case  of  an  equal 
contact  with  Urtica  urens. 

On  an  excursion  along  the  San  Felix  River,  in  eastern  Chiriqui, 
with  Dr.  MacDonald,  geologist  of  the  Canal  Commission,  the  writer 
became  acquainted  with  Jatrc  pha  urens  by  unavoidable  contact  with 
a  single  specimen  of  the  plaM.  All  at  once  he  felt  an  intense  burn- 
ing on  the  left  hand,  where  about  10  of  the  stinging  hairs  had  entered 
pretty  deep  into  the  skin.  The  inflammation  produced  by  this  touch 
was  very  similar  to  that  produced  by  nettles,  but  the  pain  soon  in- 
creased, the  whole  hand  began  to  swell  and  inside  of  half  an  hour 
had  assumed  a  monstrous  shape.  Then  the  arm  commenced  to  swell 
also,  the  right  hand  and  arm,  without  having  been  inoculated,  yet 
showed  the  same  abnormal  symptoms,  and  a  very  strong  itching 
sensation  was  felt  all  over  the  upper  part  of  the  body.  At  about 
the  same  time  parts  of  the  face,  around  the  eyes  and  nose,  swelled 


^oveXrfmT  }  To  Study  Food  and  Drug  Questions.  529 

considerably.  The  itching  sensation  rapidly  spread  over  the  abdo- 
men and  the  lower  extremities  and  red  pimples  appeared  everywhere. 
In  less  than  an  hour  the  poison  had  extended  over  the  whole  surface 
of  the  body,  and  its  entrance  into  the  blood  current  was  indicated 
by  the  corresponding  physiological  reaction  of  the  interior  organs. 
The  palpitation  of  the  heart  became  extremely  accelerated  and  the 
mind  was  soon  overcome  by  an  agonizing  depression.  The  respira- 
tion seemed  to  be  delayed  as  if  under  a  great  pressure,  cold  sweat 
broke  out,  and  the  patient  gave  way  altogether,  remaining  uncon- 
scious for  more  than  an  hour,  except  for  feverish  dreams.  After 
coming  back  to  his  senses,  he  had  several  fits  of  copious  vomiting, 
from  which  it  may  be  surmised  that  the  poison  was  slowly  elimi- 
nated from  the  organism.  The  weakness,  however,  remained  for 
several  days. 

A  case  of  such  extreme  effects,  which  might  have  killed  a  man 
of  less  strength  than  the  writer,  has  never  been  recorded,  as  far  as 
the  literature  on  the  subject  shows.  Undoubtedly  the  intensity  of 
the  intoxication  was  due  to  the  rather  strong  contact  with  the  plant, 
which  caused  a  considerable  amount  of  poison  to  be  introduced  into 
the  blood  circulation. 

Many  other  tropical  plants,  among  them  some  Urticacea?  and 
Loasaceoc,  have  such  deadly  stinging  hairs,  the  poison  of  which  is 
active  enough  to  kill  a  man,  even  in  a  relatively  small  dose.  The  only 
way  of  allaying  its  effects  would  be  to  neutralize  or  precipitate  it 
by  means  of  a  prompt  application  of  chloride  of  lime,  ammonia  or 
sodium  permanganate. 

Otto  Lutz 

Instituto  Nacional  de  Panama, 
Panama,  R.  de  P. 


UNITED  STATES  CHAMBER  OF  COMMERCE  TO  STUDY 
FOOD  AND  DRUG  QUESTIONS 

The  Chamber  of  Commerce  of  the  United  States  of  America,  a 
body  composed  of  representatives  from  about  600  local  boards  of 
trade,  chambers  of  commerce,  and  trade  associations,  widely  dis- 
tributed throughout  the  United  States,  has  taken  up  the  study  of  the 
subject  of  uniform  food  and  drug  regulation.  For  this  purpose  a 
special  committee  was  appointed  in  July,  and  its  first  meeting  was 


53°  To  Study  Food  and  Drug  Questions.  {ANoVfmbeVPih9um' 

held  at  the  headquarters  of  the  Chamber  in  Washington,  October 
8th.  The  committee  is  composed  of  Willoughby  M.  McCormick,  of 
Baltimore ;  A.  J.  Porter,  of  Niagara  Falls ;  John  A.  Green,  of  Cleve- 
land;  B.  L.  Murray,  of  New  York,  and  Theodore  F.  Whitmarsh, 
of  New  York.  Mr.  McCormick,  the  chairman,  is  a  member  of  the 
Board  of  Directors  of  the  Chamber  of  Commerce  of  the  United 
States,  and  the  head  of  the  firm  of  McCormick  &  Co.,  manufacturers 
of  extracts  and  drugs  and  importers  of  spices  and  teas ;  Mr.  Porter 
is  president  of  the  Shredded  Wheat  Company;  Mr.  Green  is  secre- 
tary of  the  National  Association  of  Retail  Grocers;  Mr.  Murray 
is  chemist  to  Merck  &  Co. ;  and  Mr.  Whitmarsh  is  vice-president  of 
Francis  H.  Leggitt-  &  Co. 

The  position  taken  by  the  committee  on  the  meaning  of  uni- 
formity is  interesting  and  will  repay  close  examination.  Its  views 
are  not  confined  to  a  limited  horizon  but  are  intended  to  grasp  the 
broader  and  wider  fields.  Its  efforts  will  be  confined  to  no  organiza- 
tion or  class  of  people.  It  hopes  to  cover  in  its  endeavors  the  posi- 
tion of  the  wholesaler,  the  retailer,  the  consumer,  the  manufacturer, 
the  official,  and  all  others  concerned  in  the  production,  handling  and 
consumption  of  food  and  drugs.  But  only  the  broad,  general  ques- 
tions of  national  character  will  be  considered.  After  a  lengthy 
discussion  the  committee  at  its  meeting,  by  unanimous  vote  of  all 
present,  adopted  the  following  regarding  uniformity : 

Uniformity,  as  the  committee  would  define  it,  involves  the  highest  degree 
of  efficiency  in  food  and  drug  control  which  it  is  possible  to  have  prevail 
universally  and  equally  in  every  part  of  the  nation.  The  Federal,  State,  and 
municipal  laws  and  their  regulations  would,  if  perfect  uniformity  were  attain- 
able, reach  the  level  of  full  and  complete  efficiency,  and  thereby  afford  equal 
protection  and  a  uniform  standard  of  living  for  all  the  people.  Uniformity 
accomplished,  places  merit  and  the  general  public  interest  over  local  political 
or  geographical  divisions.  This  committee  will,  therefore,  direct  its  efforts 
and  consideration  toward  the  accomplishment  of  uniformity.  The  committee 
cannot  but  feel  impressed  with  the  magnitude,  the  importance,  and  the  serious- 
ness of  its  work.  It  cannot  but  feel  the  need  for  the  closest  study  of  the 
subject.  And,  again,  the  committee  cannot  but  feel  the  necessity  for  the 
fullest  and  most  cordial  cooperation  between  itself  and  the  officials  and  all 
others  concerned.  The  committee  will,  of  necessity,  act  deliberately  and 
slowly,  making  certain  of  each  step,  considering  only  the  important  problems 
of 'a  national  character. 


THE  AMEKICAN 


JOURNAL  OF  PHAR: 


V 


DECEMBER,  1914.  [      Q£Q   7  19l4 


BELLADONNA  AND  HYOSCYAmi^E!^3^ 

By  Edwin  L.  Newcomb,  College  of  Pharmacy,  University  of  Minnesota. 

Part  I. — Cultivation  Experiments. 

Atropa  Belladonna  and  various  species  of  Hyoscyamus  have  been 
carefully  studied  for  some  time  and  descriptions  have  been  prepared 
by  chemical  and  botanical  workers.  Recently  some  additional  ob- 
servations have  been  made  and  work  done  by  the  writer,  the  results 
of  which  seem  of  sufficient  importance  to  present. 

Seeds  of  Atropa  Belladonna  L.  and  of  various  species  and  varie- 
ties of  Hyoscyamus  were  secured  from  various  sources  and  plants 
propagated  from  them  used  for  the  work.  In  the  securing  of  seeds 
of  H.  niger  L.  and  of  H.  albus  L.  it  was  learned  that  other  botanical 
names  were  sometimes  applied  to  these  plants  and  that  some  con- 
fusion exists  in  the  use  of  the  various  synonyms.  According  to 
the  Index  Kewensis,  the  following  named  plants  are  identical  with 
Hyoscyamus  niger  L. :  H.  agrestis  Kit.,  H.  auriculatus  Tenore, 
H.  bohemicus  F.  W.  Schmidt,  H.  lethalis  Salisb.,  H.  oiHcinarum 
Crantz,  H.  pallidus  Waldstand  Kit.,  H.  persicus  Boiss  and  Buhse, 
H.  pictus  Roth.,  H.  syspirensis  C.  Koch,  H.  verviensis  Lej.,  and 
H.  vulgaris  Neck;  and  the  following  identical  with  Hyoscyamus 
albus  L. :  H.  aureus  All.,  H.  canariensis  Ker-gawl.,  H.  Clusii  G.  Don., 
H.  luridus  Salisb.,  H.  minor  Mill.,  H.  major  Mill.,  and  H.  varians 
Vis  in  Flora.  Unquestionably  there  is  a  wide  range  of  variation  in 
H.  niger  L.  and  H.  albus  L.,  and,  while  some  of  the  above  synonyms 
probably  arose  from  the  discovery  and  naming  of  the  plants  by  in- 
dependent workers  at  about  the  same  time,  still  others  represent 


1  Presented  to  the  Philadelphia  College  of  Pharmacy  for  the  degree  of 
Master  in  Pharmacy  in  course. 

(53i) 


532 


Belladonna  and  Hyoscyamus. 


{Am.  Jour.  Pharm. 
December,  1914. 


variations  of  but  a  fraction  of  a  unit  character  from  the  type.  Then 
again  the  name  H.  agrestis  Kit.  has  been  applied  to  the  specific 
annual  form  of  H.  niger  L.  Many  of  these  early  specific  names  are 
still  more  or  less  in  use,  and,  while  one  may  secure  seeds  from  a 
number,  the  resulting  plants  conform  to  type  specimens  of  H.  niger 
L.,  H.  albus  L.,  or  to  hybrids.  Furthermore,  it  appears  to  be  quite 
impossible  at  the  present  time  to  secure  seeds  of  Hyoscyamus  which 
represent  pure  races  from  any  of  the  various  seed  dealers. 

Culture  and  Wintering. 

The  seeds  of  H.  niger  L.  biennial  germinate  in  about  the  same 
length  of  time  after  being  planted  as  do  the  seeds  of  Atropa  Bella- 
donna, most  of  the  seeds  requiring  from  four  to  six  weeks  to  come 
up,  while  a  few  may  require  much  longer.  The  seeds  of  H.  niger 
L.  annual  and  H.  albus  L.  germinate  quite  evenly  in  from  eight  to 
ten  days.  With  proper  care  the  plants  make  a  very  rapid  growth. 
No  particular  difficulty  was  experienced  in  the  cultivation  of  several 
hundred  of  each  species.-  Hyoscyamus,  however,  requires  rather 
more  attention  than  most  plants  in  connection  with  transplanting, 
spraying,  watering,  hoeing,  etc. 

The  biennial  plants  forming  the  basis  of  the  work  reported  in 
this  paper  were  protected  during  the  winters  by  the  following 
methods :  After  the  first  hard  freeze  coarse  straw  manure  about  a 
foot  deep  was  placed  over  the  garden  plots  of  Atropa  Belladonna 
and  H.  niger,  the  roots  of  a  second  lot  dug  up  and  buried  in  a  pro- 
tected location,  while  a  third  lot  of  each  were  potted  and  stored  in  a 
cold-house.  The  Belladonna  plants  all  survived  the  first  winter  ex- 
cept those  left  out  in  the  garden  plots.  During  the  second  winter 
(1912-13)  all  Belladonna  plants  survived.  The  potted  plants  of 
Hyoscyamus  were  the  only  Hyoscyamus  plants  that  survived  both 
winters.  The  lowest  outside  temperature  during  the  first  winter 
(1911-12),  as  determined  by  an  accurately  recording  thermometer 
placed  in  the  garden,  was  -33°  F.,  and  for  the  second  winter 
-22°  F. 

I  have  subjected  the  various  species  and  varieties  of  Hyoscyamus 
plants  and  Belladonna  plants  that  I  have  grown  during  the  past  three 
summers  to  varying  conditions  in  order  to  learn  more  concerning 
their  exact  nature  and  habits.  The  increased  use  of  drugs  from 
cultivated  plants  makes  such  studies  of  prime  importance,  and,  while 


Am.  Jour.  Pharm.  \ 

December,  1914.  J 


Belladonna  and  Hyoscyamus. 


533 


ecologic  and  physiologic  investigations  have  been  carried  out  with  a 
number  of  medicinal  plants,  for  the  most  part  these  studies  have  not 
been  made  with  the  object  in  view  of  securing  vegetable  drugs  of 
uniform  maximum  medicinal  values. 


The  Alternating  Annual  and  Biennial  Habit. 

In  connection  with  the  cultivation  of  Hyoscyamus  I  have  given 
some  attention  to  the  constancy  of  the  various  forms  under  observa- 


Fig.  i. — Hyoscyamus  niger,  biennial.    Portion  of  a  plot  showing  rosette  character  of  the  leaves 

and  their  long  petioles. 

tion,  to  determine  the  presence  or  absence  of  the  alternating  annual 
and  biennial  habit.  Before  giving  the  results  of  my  own  experiments 
along  this  line  I  will  briefly  discuss  the  phenomenon. 

De  Vries  states  that  in  plants  which  possess  the  alternating  annual 
and  biennial  habit  the  biennial  species  which  presents  the  character 
of  occurring  partly  in  annual  and  partly  in  biennial  specimens  must  1 
possess  the  capacity  of  growing  as  annuals  in  a  semi-latent  condi- 
tion, and  that  this  capacity  does  not  seem  to  be  universal,  but  to  be 


534 


Belladonna  and  Hyoscyamus. 


/Am.  Jour.  Pharm. 
\  December,  1914. 


confined  to  particular  races.  De  Vries  presents  experimental  evidence 
to  prove  that  biennial  species  which  possess  this  semi-latent  capacity- 
are,  in  becoming  annuals,  largely  influenced  by  external  factors. 
A  large  number  of  plants  will  become  annual  if  the  seeds  germinate 
early  or  biennial  if  their  seeds  germinate  late ;  here  the  stimulus  of 
the  spring  frost  or  cool  weather  is  in  some  cases  a  factor  which 
causes  annuals  or  bolting,  as  in  the  sugar  beet.  In  addition,  many 
plants  possess  an  inherited  variability  to  be  either  annuals  or  biennials. 


Fig.  2. — Flowering  branches  of  Hyoscyamus  niger,  annual. 


In  summing  up  experiments  on  CEnothera,  De  Vries  shows  that 
"biennial  species  which  possess  in  a  semi-latent  state  the  capacity  to 
produce  annual  specimens  can  be  induced  to  manifest  this  anomaly 
to  a  much  greater  extent  by  supplying  them  with  more  food.  Crowd- 
ing of  plants,  shading,  lack  of  manure,  or  cultivation  on  sand  favors 
the  production  of  biennials ;  but  the  more  space,  light,  and  nourish- 
ment in  the  soil  there  is  at  the  disposal  of  the  individual  plants  the 
greater  will  be  the  number  of  those  which  will  produce  stems,  flower, 
and  ripen  their  seed  the  first  summer."   Continued  selection  fails  to 


Am.  Jour.  Pharm. 
December,  1914. 


}         Belladonna  and  Hyoscyamus.  535 


fix  the  biennial  races  and  to  free  them  of  annual  species  or  to  free 
the  annual  races  of  biennial  individuals. 

Holmes,  in  considering  the  occurrence  of  annual  plants  in  the 
biennial  henbane  fields  of  England,  states  that  "the  seeds  of  the 
capsules  last  formed  are  often  deficient  in  vitality  and  the  plants 
produced  from  them  flower  the  first1  year,  hence  the  occurrence  of 
annual  plants  among  the  biennial." 

In  discussing  CEnothera  Lamar kiana  (a  plant  which  possesses  the 
semi-latent  alternating  annual  and  biennial  habit)  De  Vries  says  that 
he  found  about  the  same  number  of  annual  and  biennial  individuals 
from  the  upper  and  lower  fruits  of  the  same  spike,  and,  furthermore, 
he  draws  the  conclusion  from  his  work  on  Trifolium  pratense 
quinquej  olium  that  the  better  the  seeds  are  fed  on  the  plant  the 
greater  is  the  development  of  the  anomaly  on  the  individuals  pro- 
duced by  them.  Poor  seeds  give  rise  to  atavists,  good  ones  to  ex- 
treme variants. 

If  we  accept  the  quite  general  belief  that  perennial  and  biennial 
plants  are  of  older  origin  than  annual  plants,  then  we  cannot  con- 
sider the  annual  henbane  as  atavistic.  On  the  choice  of  seeds  in 
selection  De  Vries  states,  after  weighing  the  evidence  of  a  large 
number  of  workers,  as  well  as  his  own,  that  "when  we  are  dealing 
with  semi-latent  or,  in  general,  with  highly  variable  characters  a 
selection  of  seeds  either  by  their  size  and  weight  or  by  their  place 
of  origin  on  the  plant  is  to  be  recommended  in  many  cases,  and  the 
general  rule  seems  to  be  that  the  place  of  origin  of  the  best  seeds 
will  also  be  that  of  the  desired  variants."  There  are  some  cases  in 
which  this  rule  does  not  apply,  as  in  Trifolium  incarnatum.  In  this 
latter  plant  De  Vries  found  that  the  reverse  of  the  general  rule  held 
good,  and  the  result  of  this  work  was  so  strikingly  different  from 
all  other  that  he  leaves  the  explanation  an  open  question.  This 
occurrence  of  the  annual  form  of  Hyoscyamus  niger  in  English 
henbane  fields  is  probably  due  to  hybridization  (which  will  be 
discussed  later  in  this  paper)  rather  than  to  semi-latent  characters 
in  the  biennial  Hyoscyamus. 

I  will  now  describe  my  own  experimental  attempts  to  bring  out 
semi-latent  characters  in  Hyoscyamus.  All  plants  grown  outside 
were  cultivated  in  the  Medicinal  Plant  Garden,  College  of  Pharmacy, 
University  of  Minnesota. 


536 


Belladonna  and  Hyoscyamus. 


(Am.  Jour.  Pharm. 
\   December,  1914. 


Experimental  Planting,  191  i. 

My  first  planting,  on  February  17th,  consisted  of  a  sample  of  seed 
labeled  Hyoscyamus  niger  and  purchased  as  the  biennial  form. 
The  germination  of  this  sample  was  very  poor,  only  four  seed  giv- 
ing rise  to  plants.  On  March  17th  three  of  these  plants  continued  to 
grow  and  were  transferred  from  the  seed-pan  to  individual  pots. 
Each  plant  developed  a  rosette  of  basal  leaves  and  was  typical  of 
the  biennial  henbane.    All  three  plants  died  later  in  the  season,  due 


Fig.  3. — Flowering  branches  of  Hyoscyamus  albus. 


to  lack  of  attention  and  a  proper  understanding  of  how  the  plants 
should  be  cared  for. 

A  second  planting  of  the  seed  referred  to  above  was  made  on 
March  17th,  and  in  twenty-four  days  a  few  seed  had  germinated. 
Fifteen  plants  were  secured  from  this  second  planting,  and  these  were 
transferred  to  a  sandy  loam  plot  in  the  medicinal  plant  garden  as 
soon  as  danger  of  frost  was  over.  The  soil  or  other  conditions 
seemed  unsuited  for  the  plants,  and  they  made  very  little  growth  after 
being  planted  out.  A  long  hot  spell  resulted  in  all  plants  dying. 
Each  plant  produced  a  weak  rosette  of  basal  leaves,  but  there  was  no 
tendency  for  the  development  of  a  shoot. 


ADeJZeVPih9ir4m"}        Belladonna  and  Hyoscyamus.  537 

The  second  sample  experimented  with  in  191 1  consisted  of  a  lot 
of  seed  purchased  as  the  drug  Hyoscyamii  Semen.  Some  of  these 
seed  were  sown  on  February  22nd  and  a  second  lot  on  March  26th. 
Both  plantings  required  about  three  weeks  to  germinate.  From  these 
plantings  seventy  plants  were  secured  and  transferred  to  flats  con- 
taining good,  rich  potting  soil.  The  plants  all  made  rapid  growth  and 
began  to  send  up  flowering  shoots  in  about  three  weeks.  The 
characteristic  rosette  of  basal  leaves  of  the  biennial  plant  was  not 
present  in  a  single  specimen.  All  of  the  plants  flowered  before  the 
weather  was  suitable  for  outside  planting,  and,  although  the  plants 
were  small,  they  represented  typical  annual  Hyoscyamus  niger. 

On  April  26th  seed  of  Hyoscyamus  niger,  H.  albus,  and  H.  pictus 
were  sown  in  cold  frames.  These  all  germinated  in  from  eight  to 
ten  days,  and  H.  albus  coming  up  first.  The  soil  in  the  seed  beds  was 
very  light  and  sandy.  No  fertilizer  whatever  was  applied.  All  of 
these  plants  were  allowed  to  remain  in  the  cold  frames,  the  sash 
being  permanently  removed  as  soon  as  danger  of  frost  was  over. 
The  plants  were  crowded  in  rows,  and  the  rows  were  close  together.. 
Other  larger  growing  plants  around  the  cold  frames  soon  placed  the 
Hyoscyamus  in  quite  dense  shade.  The  conditions  affecting  the 
growth  of  the  plants  throughout  the  season  were  such,  that  had  semi- 
latent  biennial  characters  been  present  in  any  of  the  plants  one  would 
have  looked  for  a  large  number  of  biennial  forms.  The  result  of 
the  experiment,  however,  was  that  every  one  of  about  two  hundred 
plants  in  each  row  sent  up  the  flower  stalk,  produced  flowers,  and 
fruited. 

Experimental  Planting,  1912. 

The  first  planting  in  1912  was  done  on  March  2nd,  and  consisted 
of  three  lots  of  seed  freshly  imported  from  Germany  and  labeled 
as  Hyoscyamus  niger,  H.  albus,  and  H.  pictus.  I  secured  a  good, 
even  germination  from  each  of  these  trials  in  two  weeks'  time. 
About  seventy-five  plants  of  each  lot  were  transferred  to  flats  the 
1st  of  April,  and  to  three-inch  pots  May  14th.  Two  weeks  later 
they  were  planted  out  in  the  open  garden,  being  placed  in  plots  of 
two  different  kinds  of  soil.  One-half  of  the  three  species  were  placed 
in  a  very  light  sandy  loam  and  the  other  half  in  soil  consisting 
of  light  sandy  loam  mixed  with  about  equal  parts  of  rich,  well- 
rotted  peat  and  other  humus.  All  of  the  plants  made  a  good,  con- 
tinual growth  from  the  time  the  seeds  germinated  until  maturity, 


538 


Belladonna  and  Hyoscyamus. 


J  Am.  Jour.  Pharm. 
I    December,  1914. 


and  all  plants  produced  flower  stalks,  flowers,  and  fruits  without 
showing  any  signs  of  the  biennial  character. 

The  second  planting  for  this  season  was  made  on  March  14th, 
and  consisted  of  a  sample  of  seed  labeled  Henbane  and  purchased 
for  the  biennial  form.  This  sample  germinated  unevenly,  but  a 
fairly  large  proportion  of  the  seed  had  started  to  grow  by  April 
10th.  About  fifty  of  the  plants  grown  from  this  lot  of  seed  were 
placed  in  flats  on  April  24th,  and  the  latter  part  of  May  they  were 
transferred  to  the  open,  twenty-five  of  the  plants  being  placed  in  a 
sandy  loam  mixed  with  an  equal  amount  of  peat  humus,  and  the  re- 
maining twenty-five  in  a  plot  the  soil  of  which  consisted  of  about 
one  foot  of  clean  sandy  loam  underlaid  with  cinders  and  sand. 
All  of  the  plants  made  a  good  growth  and  were  all  characterized  by 
the  numerous  typical  basal  leaves  of  the  biennial  henbane.  The 
plants  were  watered  by  city  water  with  a  hose  when  rain  was  not 
sufficient.  Most  of  the  plants  in  the  sand  underlaid  with  cinders 
died  during  the  latter  part  of  the  summer,  when  it  was  exceedingly 
hot.  Those  plants  in  the  richer  soil,  however,  continued  to  grow 
luxuriantly,  and  by  fall  many  of  them  were  two  feet  across.  None 
of  the  plants  under  either  condition  showed  any  sign  of  producing 
flower  stalks. 

The  third  planting,  on  March  21st,  19.12,  consisted  of  a  fresh 
sample  of  seed  labeled  Hyoscyamus  niger  and  obtained  from  Ger- 
many. In  this  planting  germination  was  very  poor,  only  eighteen 
plants  being  obtained,  and  the  seed  which  produced  these  few  plants 
required  from  three  to  four  weeks  to  germinate.  All  of  these  plants 
grew  rapidly,  produced  flowers  and  fruits,  but  did  not  show  the 
biennial  habit  in  any  respect,  although  they  were  not  grown  under 
the  most  favorable  conditions. 

Experimental  Planting,  1913. 

All  planting  of  Hyoscyamus  seed  in  the  spring  of  191 3  was 
done  on  February  7th,  at  which  time  five  different  lots  of  seed  were 
sown. 

Lot  number  one  and  lot  number  two  were  each  bought  for 
Hyoscyamus  niger,  biennial.  The  seed  of  these  two  lots  germinated 
quite  evenly,  requiring  from  four  to  five  weeks  to  come  up.  Twenty 
plants  from  each  lot  were  placed  in  separate  flats  with  rich  potting 
soil  on  March  20th,  where  they  continued  to  grow  for  about  three 


A"eeembeVPi9um'}        Belladonna  and  Hyoscyamus. 


539 


weeks.  The  plants  were  then  put  into  three-inch  pots,  where  they 
were  held  until  transferred  to  the  garden,  early  in  May.  All  of  the 
plants  were  placed  in  a  plot  in  which  the  soil  was  composed  of  very 
rich  garden  loam.  A  late  spring  frost  injured  many  of  the  plants, 
but  they  soon  recovered  and  made  a  vigorous  growth  throughout  the 
summer.  Each  plant  produced  a  large  rosette  of  basal  leaves,  but 
not  a  single  plant  showed  any  tendency  to  develop  the  flowering  stalk. 
The  third,  fourth,  and  fifth  lots  of  seed  sown  in  the  spring  of 


Fig.  4. — Flowers  of  Hyoscyamus  niger,  annual. 


1913  were  freshly  imported  from  Germany  and  were  labeled  re- 
spectively as  follows :  Hyoscyamus  niger,  H.  albus,  and  H.  pictus. 
In  each  lot  germination  took  place  in  about  ten  days.  Seventy-five  to 
ninety  plants  from  each  lot  were  transferred  to  flats  as  soon  as  the 
second  pair  of  leaves  were  well  formed.  When  the  plants  became 
crowded  in  the  flats  they  were  placed  into  three-inch  pots.  The 
plants  grew  rapidly  and  many  had  produced  flowers  by  the  time 
they  were  planted  in  the  garden,  which  was  early  in  May.  Most  of 
the  plants  were  placed  in  pots  in  which  the  soil  was  quite  rich,  and 


54o 


Belladonna  and  Hyoscyamus. 


J  Am.  Jour.  Pharm. 
|   December,  1914. 


within  a  short  time  every  plant  had  produced  a  flower  stalk,  flowers, 
and  fruit.  The  plants  continued  flowering  throughout  the  early 
summer  and  then  died. 

The  results  of  these  experiments,  in  so  far  as  semi-latent 
characters  are  concerned,  may  be  summarized  in  a  very  few  lines. 
Altogether  over  twelve  hundred  plants  were  grown,  and  these  were 
subjected  to  a  number  of  varying  conditions,  with  the  result  that 
not  a  single  plant  showed  any  tendency  to  change  from  the  annual 
to  the  biennial  form  or  from  the  biennial  to  the  annual  form. 
While  these  experiments  are  probably  not  conclusive,  they  indicate 
that  pure  races  probably  exist  of  the  annual  and  biennial  forms  of 
Hyoscyamus. 

Hybridization. 

The  work  which  I  have  thus  far  done  has  not  included  any  ex- 
perimental crossing  of  the  different  species  and  varieties  of 
Hyoscyamus,  but  in  the  attempt  to  secure  pure  species  and  races 
for  later  work  some  observations  have  been  made  which  seem  worthy 
of  mention.  Throughout  the  cultivation  of  Hyoscyamus  it  has  been 
noted  that  the  amount  of  pigment  in  the  flowers  was  exceedingly 
variable.  In  Hyoscyamus  there  are  two  distinct  color  units,  which 
may  be  termed  physiologic  units.  The  first  of  these  is  represented 
by  anthocyanin,  to  which  is  due  the  dark  coloring  of  the  veins  of 
Hyoscyamus  niger,  and  the  second  is  a  yellow  element.  During  the 
past  season,  when  several  hundred  plants  of  Hyoscyamus,  grown 
from  commercial  seed  supplies,  were  under  cultivation,  I  arranged 
twenty  plants,  each  with  a  slightly  varying  amount  of  color,  in  such 
an  order  as  to  represent  at  the  one  end  a  typical  specimen  of  H.  niger 
with  the  maximum  amount  of  anthocyanin,  while  at  the  other  end 
of  the  row  a  plant  difficult,  if  not  impossible,  to  distinguish  from 
typical  H.  albus.  This  condition  appears  to  be  explained  by  the 
somewhat  extended  experiments  on  the  hybridization  of  different 
species  and  forms  of  Hyoscyamus  by  De  Vries  and  by  C.  Correns. 
From  the  results  of  these  experiments  it  is  shown  that  H.  niger  var. 
annual  readily  crosses  with  H.  albus,  and  that  the  anthocyanin  is  a 
dominant  character.  Crosses  between  H.  niger  annual  and  H.  niger 
biennial  have  also  been  made,  and  in  such  crosses  the  biennial  form 
appears  to  dominate.  The  pedigree  of  the  crosses  conforms  to  the 
laws  of  Mendel,  even  when  the  experiments  have  been  carried  into 
the  third  generation. 


\m.  Jour.  Pharm. 
December,  1914. 


Belladonna  and  Hyoscyamus. 


54i 


Pollination  in  Hyoscyamus  plants  not  under  experimental  control 
takes  place  partly  by  means  of  insects  carrying  pollen  from  the 
flowers  of  one  lot  of  plants  to  the  flowers  of  other  plants  which  may 
be  of  a  different  variety  or  form.  This  gives  rise  to  vicinists,  and 
hence  seed  supplies  from  field-grown  or  wild  plants  collected  where 
several  forms  are  growing  together  will  not  infrequently  produce 
hybrids  rather  than  pure  species  or  varieties.  And  for  the  same 
reason  commercial  seed  supplies,  unless  obtained  from  plants  grown 
under  control  or  from  plants  grown  in  isolated  districts,  will  not 


Fig.  5. — Flowers  of  Hyoscyamus  albus. 


always  yield  pure  races.  Furthermore,  it  should  be  pointed  out  that 
H.  albus  is  probably  not  an  elementary  species,  but  rather  a  retro- 
grade variety  of  //.  niger,  in  which  the  unit  character  anthocyanin 
is  more  or  less  latent.  This  difference  between  elementary  species 
and  certain  systematic  species  has  been  fully  discussed  by  De  Vries, 
and  the  importance  of  a  physiological  classification  based  upon 
physiological  units  should  not  be  underestimated  by  those  engaged 
in  medicinal  plant  breeding.  To  illustrate  the  difference  between  an 
elementary  species  and  a  systematic  species  or  variety,  De  Vries 


542  Standardisation  of  Commercial  Papain.  {ADecemYerPi9i4m' 

calls  attention  to  Datura  Tatula  and  Datura  Stramonium,  in  which 
every  analogy  points  to  the  blue  as  the  older  and  the  white  as  the 
younger  form  or  retrograde  variety.  Atropa  Belladonna  lutea  is 
another  example  of  a  plant  where  the  physiologic  unit  anthocyanin 
is  lost  or  latent,  and  this  plant  we  consider  as  a  variety  of  Atropa 
Belladonna.  The  actual  proof  of  the  relationship  between  elementary 
species  and  varieties  is,  of  course,  rarely  to  be  obtained. 

From  this  brief  discussion  on  hybridization  and  the  principles 
involved  it  seems  most  probable  that  the  occasional  annual  forms 
of  Hyoscyamus  in  the  biennial  henbane  fields  of  England  is  due  to 
natural  hybridization. 

At  this  time  I  desire  to  call  attention,  first,  to  the  importance  of 
the  determination  of  the  exact  nature  of  the  plant, — i.e.,  whether  it 
represents  an  elementary  species,  a  variety,  a  hybrid,  a  constant  or 
an  inconstant  form;  and,  second,  to  the  need  for  close  and  critical 
study  of  the  medicinally  active  constituents  as  physiologic  units. 
Following  this,  selection  and  hybridization  for  the  purpose  of  pro- 
ducing better  drugs  may  proceed  along  scientific  lines  and  inter- 
changes or  combinations  of  desired  unit-characters  formed. 

{To  be  continued.) 


STANDARDIZATION  OF  COMMERCIAL  PAPAIN. 
By  F.  W.  Heyl,  C.  R.  Caryl,  and  J.  F.  Staley. 

The  term  "papain"  is  supposed  to  describe  an  especially  prepared 
product  containing  the  enzymatic  constituents  in  greater  propor- 
tion, and  hence  having  a  higher  digestive  activity,  than  the  crude 
juice.  Thus,  in  Merck's  "  Index  "  papain  is  described  as  having  a 
digestive  power  on  blood  fibrin  of  I  :  200,  whereas  the  proteolytic 
activity  of  the  dried  juice  is  only  1  :  80.  For  the  latter  determina- 
tion no  method  of  standardization  is  suggested,  although  the  fibrin 
test  is  probably  understood. 

The  fibrin  test  is  decidedly  awkward  and  inelegant.  Further- 
more, there  are  some  important  disagreements  as  to  the  conditions 
under  which  the  test  should  be  carried  out.  In  Hager's  "Handbuch 
der  Pharmaceutischen  Praxix"  this  test 1  is  described  as  being 
carried  out  in  a  medium  made  slightly  alkaline  with  sodium 


^and  1,  640. 


ADecSerPih9Hm'}^^aw^af^^a^ow  °f  Commercial  Papain.  543 

hydroxide,  and  that  the  fibrin  is  acted  on  for  from  four  to  five  hours 
at  450  to  500  C.  It  is  there  further  stated,  however,  that  the  products 
of  several,  different  manufacturers  vary  as  to  their  activity  in  acid 
and  alkaline  medium  respectively.  Thus  it  is  stated  that  the  prep- 
arations of  E.  Merck  and  of  Gehe  &  Co.  acted  best  in  alkaline 
medium,  while,  on  the  other  hand,  those  of  Boehringer  and  of 
Finkler  were  active  in  acid  solution. 

The  fibrin  test  has  been  little  used  in  this  country  because  of  the 
doubtfulness  of  the  method  and  because  cff  the  experimental  diffi- 
culties involved  in  carrying  it  out.  During  recent  years  our  litera- 
ture contains  several  contributions  dealing  with  assay  methods  which 
are  more  Serviceable  than  the  assay  by  means  of  fibrin. 

However,  during  the  period  in  which  these  newer  methods  were 
being  evolved  the  commercial  product  has  been  adulterated  to  a 
shameful  extent,  and  the  terms  "papain"  and  "pawpaw  juice"  are  not 
now  characteristic  of  two  different  products.  Indeed,  papain  now 
really  signifies  dried  pawpaw  juice.  We  have  found  no  products 
on  the  market  having  a  higher  digestive  strength  than  has  dried 
pawpaw  juice,  although  the  terms  "papain,"  "purified  papain,"  "con- 
centrated active  principle,"  etc.,  were  used  in  describing  some  of  the 
various  products.  Some  of  these  were  offered  for  greatly  advanced 
prices,  in  one  case  the  price  per  pound  being  almost  $10.  Official 
recognition  of  this  product,  as  well  as  a  method  for  standardization, 
is  very  desirable. 

Among  the  newer  methods,  we  have  one  described  by  Graber.2 
This  method  is  that  of  allowing  10  grammes  of  properly  prepared 
round  steak  to  stand  with  0.325  gramme  of  papain  in  the  presence  of 
85  c.c.  of  0.3  per  cent,  hydrochloric  acid  at  520  C.  for  six  hours-. 
The  undigested  portion  should  not  measure  more  than  2  c.c.  in  a 
graduated  settling  tube.  The  proteolytic  activity  then,  under  these 
conditions,  is  I  > :  30.  Graber  describes  the  results  obtained  by  this 
method  in  studying  the  activity  of  pawpaw  juice,  but  not  of  com- 
mercial papain.  He  found  the  proteolytic  activity  on  steak  to  be 
greatest  in  a  0.3  per  cent,  hydrochloric  acid  medium. 

Horace  North  3  examined  twelve  samples  of  commercial  papain, 
six  of  which  proved  by  his  method  to  be  inactive.  The  experimental 
values  showing  the  comparative  activity  of  the  six  genuine  samples 


2  Jour.  Ind.  and  Eng.  Chem.}  3,  919  (1911). 

6  Report  of  Lehn  &  Fink's  Analytical  Department,  1910-1912,  p.  66. 


544  Standardisation  of  Commercial  Papain.  { December 'wu"' 

are  not  given.  North  does  not  state  whether  or  not  the  active 
samples  contained  any  starch,  although  this  adulterant  was  noted 
by  him  in  the  valueless  samples.  North  used  the  test  which  is  official 
for  pepsin.  A  residue  of  36  c.c.  is  obtained  from  ten  grammes  of 
coagulated  egg-albumin.  In  the  assay  0.05  gramme  of  papain  is 
allowed  to  act  on  ten  grammes  of  albumin.  After  digestion  with  a 
good  sample  of  papain  a  residue  of  only  6  c.c.  remains.  In  his 
calculations  North  allows  for  a  blank  of  1  c.c,  exactly  as  in  the  U. 
S.  P.  method  for  pepsin.  The  proteolytic  activity  then  was  cal- 
culated as  follows :  There  remained  6-1  or  5  c.c.  of  albumin  after 
the  digestion,  hence  30  c.c.  was  digested.  The  proteolytic  ratio, 
therefore,  was  ft  or  ?.  If  the  papain  had  digested  the  10  grammes 
completely,  the  proteolytic  ratio  would  have  been  1  :  200.  In  this 
case,  then,  the  ratio  was  1  :  171.  This  ratio,  like  the  one  given  by 
Graber,  is  for  digestion  in  an  acid  medium. 

Rippetoe4  assayed  papain  by  using  40  c.c.  of  a  0.1  per  cent, 
sodium  hydroxide  solution,  10  grammes  of  egg-albumin  (prepared 
as  directed  in  the  U.  S.  P.),  and  by  carrying  out  the  digestion  at 
520  C.  for  six  hours.  The  quantity  of  papain  used  was  0.1  or  0.2 
gramme.  The  residue  left  after  digestion  was  transferred  to  a 
graduated  cylinder  and  the  final  volume  made  up  to  70  c.c.  The 
proteolytic  activity  was  indicated  by  the  fact  that  digestion  with 
0.1  gramme  papain  left  a  residue  of  18  c.c,  while  a  blank  measured 
43  c.c  Other  experiments  described  by  Rippetoe  show  the  in- 
hibiting action  of  hydrochloric  acid  when  present  in  quantities  of 
0.2  per  cent,  or  0.3  per  cent. 

H.  M.  Adams  5  again  calls  attention  to  the  presence  of  starch, 
and  points  out  the  fact  that  pepsin  may  be  detected  by  making  a 
quantitative  digestion  of  beef  in  the  presence  of  0.2  per  cent,  hydro- 
chloric acid.  Adam's  method  of  assay  is  identical  with  that  de- 
scribed by  Graber,  except  that  the  medium  employed  is  neutral  in- 
stead of  acid.  Results  are  given  showing  the  inhibiting  action  of 
0.3  per  cent,  hydrochloric  acid. 

In  a  recent  paper  F.  F.  Shelley  6  has  applied  a  modification  of 
Sorensen's  method,  and  offers  a  standard  for  pawpaw  juice  on  the 


*Jour.  Ind.  and- Eng.  Chem.,  4,  517  (1912). 
6  Jour.  Ind.  and  Eng.  Chem.,  6,  669  (1914). 
8  Analyst,  39,  170. 


December,  lii™' }  Standardization  of  Commercial  Papain.  545 

basis  of  the  quantitative  formation  of  carboxyl  groups  when  casein  is 
digested  in  slightly  alkaline  solution.  R.  Delaumay  and  O.  Bailly  7 
state  that  papain  is  a  peptone- forming  enzyme.  They  find  that  there 
is  no  relation  between  the  proteolytic  and  milk-coagulation  powers 
of  papain.  They  recommend  that  the  method  of  assay  be  based  on 
the  amount  of  protein  dissolved  in  unit  time. 

The  work  which  has  been  done  in  this  laboratory  for  the  pur- 
pose of  standardization  is  based  upon  the  work  of  Mendel  and 
Blood,8  and  a  number  of  commercial  samples  have  been  examined 
with  the  methods  there  given.  We  will  therefore  outline  the  methods 
used,  tabulate  our  results,  and,  lastly,  state  our  conclusions  at  the 
end  of  the  paper. 

Experimental. 

The  methods  other  than  those  used  in  studying  the  proteolytic 
activity  were  those  of  the  Official  Agricultural  Chemists.9  The 
directions  for  the  protein  digestions  were  as  follows : 

Preparation  of  Solutions. —  (a)  Egg-white  solution.  Separate 
the  whites  of  six  freshly-laid  eggs  and,  after  beating  slightly,  dilute 
with  two  volumes  of  1  per  cent,  sodium  chloride  solution.  Mix. 
Filter  through  plaited  filter  paper.  Make  up  to  a  definite  volume  10 
and  mix  thoroughly. 

(b)  Weigh  one  gramme  of  the  papain  and  transfer  to  a  dry 
100  c.c.  graduated  flask.  Do  not  make  up  the  solution  until  every- 
thing is  ready  for  the  determination.  The  papain  is  then  taken  up 
with  1  per  cent,  salt  solution,  shaken  thoroughly,  and  made  exactly 
to  volume.  Exactly  30  minutes  should  elapse  from  the  time  the  salt 
solution  is  poured  upon  the  papain  until  the  aliquots  of  the  solution 
are  taken. 

(c)  N/2  acetic  acid. 

Determination  of  Proteolytic  Activity  at  8o°  to  ioo°  C. — Into  a 
clean,  dry  50  c.c.  Erlenmeyer  flask  place  15  c.c.  of  standardized  egg- 
white  solution,  add  1  c.c.  of  the  papain  solution  and  then  9  c.c.  of 
1  per  cent,  salt  solution.  All  the  digestions  are  made  in  a  volume  of 
25  c.c.    Transfer  at  once  to  the  thermostat,  already  regulated  at 

7  Bull.  Sci.  Pharmacology,  20,  141-7  (1913). 

8  Jour.  Biol.  Chem.,  viii,  177  (1910). 

0  U.  S.  Dept.  Agr.  Bur.  of  Chem.  Bull.  107  (revised). 

10  This  solution  should  be  so  made  that  15  c.c.  contains  0.4000  gramme 
coagulable  protein.  This  requires  a  preliminary  determination  and  subse- 
quent dilution. 


546  Standardisation  of  Commercial  Papain.  {ADeoSrPwS1' 

80 °  C,  and  allow  the  digestion  to  proceed  for  exactly  15  minutes. 
Now  add  1  ex.  of  N/2  acetic  acid  and  transfer  immediately  to  a 
bath  at  ioo°  C.  and  heat  for  ten  minutes.  The  time  factor  should  be 
given  the  sharpest  attention. 

Bath  at  8o°  C. — 15  minutes. 

Transfer — 1  minute. 

Bath  at  ioo°  C. — 10  minutes. 

In  order  to  faciliate  the  acidification,  a  two-holed  stopper  is  used, 
bearing  a  long  glass  tube  to  serve  as  a  condenser,  and  a  small 
funnel  into  which  1  c.c.  of  acetic  acid  can  be  easily  placed. 

The  undigested  protein  is  filtered  off  on  a  tared  filter  paper. 
Wash  free  from  chlorides.  Wash  with  10  c.c.  of  95  per  cent, 
alcohol,  and  when  this  has  passed  through  add  10  c.c.  of  ether  U. 
S.  P.    Dry  at  ioo°  to  105 0  to  constant  weight. 

At  the  same  time  that  the  above  digestion  is  carried  out,  the 
amount  of  protein  in  the  egg-white  solution  coagulable  by  heat  is 
determined  in  a  blank,  i.e.,  15  c.c.  of  the  same  egg-white  solution 
is  mixed  with  10  c.c.  salt  solution  (or,  better,  9  c.c.  salt  solution  and 
1  c.c.  of  the  papain  solution  in  which  the  enzyme  has  been  destroyed 
by  boiling  vigorously  for  15  minutes)  and  the  operations  are  carried 
out  upon  this  mixture  exactly  as  described  above. 

Calculate  the  percentage  of  protein  rendered  non-coagulable  under 
these  conditions. 

Test  for  Pepsin  in  Papain. — Take  15  c.c.  of  the  same  egg-white 
solution  as  prepared  for  the  first  digestion.  Add  2  c.c.  1  per  cent, 
salt  solution,  3  c.c.11  of  N/2  HQ  and,  lastly,  5  c.c.  of  a  1  per  cent, 
papain  solution.  Add  0.5  c.c.  toluol  to  prevent  putrefaction.  Digest 
at  400  C.  for  15  hours.  Add  25  c.c.  of  a  10  per  cent,  solution  of 
trichloracetic  acid.  Heat  to  boiling  on  an  electric  stove.  Boil  ten 
minutes  and  filter  through  a  tared  paper,  and  wash  the  coagulum 
free  from  acid.  Wash  with  alcohol  and  ether.  Dry  at  ioo°  to 
1050  C.  to  constant  weight.  At  the  same  time  that  this  digestion  is 
carried  out  the  total  amount  of  coagulable  protein  present  should 
be  determined  in  a  blank  experiment. 


11  For  the  determination  of  the  proteolytic  activity  at  a  concentration  of 
0.5  per  cent.  Na,C03,  3  c.c.  of  a  sodium  carbonate  solution  (containing 
0.125  gramme  Na2COs)  was  used  instead  of  the  N/2  hydrochloric  acid. 
For  the  determination  of  the  proteolytic  activity  at  the  alkalinity  of  the'  egg 
3  c.c.  of  salt  solution  was  used. 


Ad  VJmberPi9ai4m' }  Standardization  of  Commercial  Papain. 


547 


Calculate  the  percentage  of  protein  digested  under  these  con- 
ditions. 

Tryptophane  Test  No.  i. — 5  c.c.  of  5  per  cent.  Witte's  peptone 
in  1  per  cent,  salt  solution,  5  c.c.  of  1  per  cent,  papain  extract  in  1 
per  cent,  salt  solution  (toluene,  1  drop).  Add  1.2  c.c.  1.71  per  cent. 
HCN  solution,  and  1.2  c.c.  N/10  hydrochloric  acid;  total  volume, 
12.4  c.c.  Digest  in  glass-stoppered  bottles  for  17  hours  at  360  to 
400  C.    Add  bromine  water  drop  by  drop. 

Tryptophane  Test  No.  2. — 5  c.c.  of  5  per  cent.  Witte's  peptone 
digested  with  5  c.c.  1  per  cent,  papain  solution  and  1  c.c.  HCN 
(1.71  per  cent.)  at  8o°  C.  for  15  minutes  should  give  a  strong 
tryptophane  test  with  bromine  water.  Report  the  intensity  of  the 
color  in  the  following  comparative  terms :  Faint,  distinct,  marked, 
strong,  deep. 

Examination  of  Fictitious  Sample. — An  apparently  fraudulent 
sample  gave  the  following  analytical  results :  Digestion  at  80 0  C, 
none;  at  360  to  400  C.  in  0.2  per  cent,  hydrochloric  acid,  61.0  per 
cent,  and  63.0  per  cent. ;  at  360  to  400  C,  at  the  alkalinity  of  egg, 


Table  I. 

Examination  of  Samples  of  Dried  Pawpaw  Latex  Containing  no  Diluents. 


Laboratory  No  

3035 

3044 

304S 

3ii7 

3039 

3040 

3328 

Digestion  at  8o°  C,  blank. 

0.424 
0.174 
58.9 

0.417 
0.236 
43-4 

0.417 
0.228 
45'- 3 

0.403 
0.169 
58.1 

0.407 
0.180 
55-7 

0.407 
0.193 
52.1 

0.394 
0.165 
58.1 

Digestion  at  360  to  400  C.  : 
(a)  0.2  per  cent.  HC1, 
blank  

Residue  

Per  cent,  digested  

0.421 
0.433 
None 

0.417 
0.407 

'  2.4 

0.434 
0.432 
None 

0.429 
0.421 
1.8 

0-439 
0.426 
2.9 

o.434 
0.431  1 
None 

0.414 
0.424 
None 

(b)   Alkalinity  of  egg, 

blank  

Residue  

Per  cent,  digested  

0.436 
0.418 
4.1 

0.417 
0.401 
3-7 

0.427 
0.406 
2.6 

0.410 
0.405 

1.2 

0.425 
0.419 
1.4 

0.421 
0.423 
None 

0.432 
0.433 
None 

(c)  0.5  per  cent.  Na2C03, 
Per  cent,  digested  

0.435 
0.434 
None 

0.416 
0.432 
None 

0.427 
0.433 
None 

0.410 
0.413 
None 

0.425 
0.430 
None 

0.421 
0.436 
None 

0.414 
0.417 
None 

Tryptophane  test,  400  C. . 
Tryptophane  test,  8o°  C. 

Nitrogen  

Starch  

Ash  

Sugars,  reducing  

Sugars,  non-reducing  

Strong 
Deep 
9.51 
None 
6.56 

10.13 
None 
None 

Deep 
Marked 

9.87 
None 

7.13 
11.23 
None 
None 

Strong 
Strong 
9.87 
None 
7-33 
11. 12 
None 
None 

Strong 
Strong 
9.98 
None 
7.38 
11.50 
None 
None 

Strong 
Marked 
9-59 
None 
9.21 
9.28 
None 
None 

Strong 
Strong 
9,88 
None 
10. 11 
9.62 
None 
None 

Strong 
Marked 

9.89 
None 
13.87 

5.10 
None 
None 

548 


Standardisation  of  Commercial  Papain.  'JS™ 


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^S^mbeV^i™'}  Standardization  of  Commercial  Papain. 


549 


there  was  no  digestion,  and  the  same  result  was  obtained  when  the 
digestion  was  carried  out  in  a  medium  of  0.5  per  cent.  Na2Co3.  It 
gave  negative  tryptophane  tests  under  both  conditions.  Nitrogen, 

Table  III. 

Examination  of  Papain  Samples  Containing  Sugar  as  Diluent. 


3118 

3037 

3083 

0.400 
0.274 
3i.5 

0.399 
0.298 
25-3 

0.421 
0.327 
22.3 

Digestion  at  360  to  400  C: 

(ot)  0.2  per  cent.  HC1,  blank. .  . 

0.214 
49-3 

0.215 
47-2 

0.216 
47-0 

(b)  Alkalinity  of  egg,  blank..  .  . 

O.428 
0.422 
1.4 

0.407 
0.401 
1-5 

0.438 
0.435 
None 

(c)  0.2  per  cent.  Na2C03,  blank 
Residue  

O.428 
O.423 
1.0 

0.408 
0.410 
None 

0-439 
0.440 
None 

Per  cent,  digested  

Tryptophane  test,  400  C  

Tryptophane  test,  8o°  C  

Distinct 
Faint 

5-79 
None 

4.14 

9-95 
24-75 

Marked 
Faint 
6.15 
None 

4.11 

24.5 

Distinct 
Faint 
5-8i 
None 

4.21 
25.65 

Ash  

1  Calculated  as  lactose. 


1.3  per  cent,  and  1.34  per  cent.;  starch,  none ;  moisture,  9.59  per 
cent. ;  ash,  4.05  per  cent.  Reducing  sugar  was  determined  after  in- 
version with  hydrochloric  acid,  and  when  calculated  as  glucose 
amounted  to  73.75  per  cent. 

SUMMARY. 

1.  In  these  digestions  with  pawpaw  juice  it  has  again  been  shown 
that  the  digestion  proceeds  rapidly  at  8o°  to  ioo°  C.  This  character- 
istic property  can  be  utilized  for  the  standardization  of  commercial 
papain  samples. 

2.  Under  the  conditions  outlined  above,  dried  pawpaw  juice 
should  be  capable  of  dissolving  at  8o°  to  ioo°  C.  not  less  than  40  per 
cent,  of  the  egg-albumin  taken. 

3.  No  samples  of  "papain"  were  found  upon  the  market  which 
had  a  higher  digestive  activity  than  the  samples  of  dried  pawpaw 
latex  under  the  conditions  employed. 


550  Pure  Drugs  and  the  Public  Health.  {^JS^r^it' 

4.  Since  the  use  of  the  term  "papain"  has  given  rise  to  the  con- 
ditions pointed  out  in  this  paper,  we  are  inclined  to  the  view  that 
papain  products  ought  to  be  marketed  as  "dried  pawpaw  juice," 
and  that  only  a  lower  limit  of  digestive  strength  should  be  stated  in 
defining  a  standard  for  it.  A  definition  proposed  upon  this  basis 
might  be  stated  as  follows  :  Dried  pawpaw  juice  is  the  dried  albumin- 
ous exudate  of  the  fruit  of  Carica  Papaya.  L.  (Fam.  Papayacese), 
free  from  starch,  sugars,  and  diluents,  and  contains  a  proteolytic 
enzyme  or  enzymes.  When  assayed  by  the  method  above 12  it 
has  the  power  of  digesting  at  8o°  to  ioo°  C.  not  less  than  40  per  cent, 
of  the  unaltered  egg-white  protein. 

5.  Of  twenty-six  samples  studied,  seven  represented  the  un- 
diluted dried  latex,  fifteen  contained  starch  in  amounts  varying 
from  15  per  cent,  to  58  per  cent.,  while  three  were  diluted  with 
sugar  and  one  with  dextrin.  Four  samples  showed  a  high  digestive 
strength  under  conditions  favorable  for  pepsin  digestion.  On  the 
basis  of  the  standard  proposed  above,  twelve  samples,  or  44  per 
cent.,  have  been  diluted  to  such  an  extent  that  their  digestive  strength 
is  below  a  very  reasonable  requirement. 
Chemical  Research  Laboratory  of  the  Upjohn  Company, 

Kalamazoo,  Mich. 


PURE  DRUGS  AND  THE  PUBLIC  HEALTH.* 
By  Martin  I.  Wilbert. 
Assistant  in  Pharmacology,  Hygienic  Laboratory,  United  States  Public 

Health  Service. 

Food  and  drug  laws  are  generally  recognized  as  being  economic 
measures  designed  to  prevent  dishonest  practices  or  gross  adultera- 
tion and  thereby  secure  to  the  purchaser  an  equitable  return  and  the 
assurance  that  the  food  or  drug  product  purchased  will  be  true  to 
name  or  nature  as  represented  by  the  seller.  The  pure  drug  features 
of  these  laws,  however,  combined  with  the  laws  designed  to  restrict 
the  practice  of  pharmacy  to  specially  trained  and  capable  individuals, 
also  have,  or  should  have,  an  evident  bearing  on  public  health  in  that 
the  purchaser  is  led  to  assume  that  the  licensed  druggist  is  directly 
responsible  for  the  character  and  purity  of  the  drugs  sold. 


12  See  page  545- 

*  Reprinted  from  the  Public  Health  Reports,  vol.  29,  No.  19,  May  8,  1914. 


ADeceSVPih9ir4m"}    Pure  Dru9s  and.  the  Public  Health.  551 

The  methods  adopted  for  enforcing  these  laws  in  the  past  have  not 
always  been  in  accord  with  the  securing  of  the  best  results  from  a 
public-health  point  of  view,  and  even  in  States  where  the  control  of 
laws  regulating  the  nature  and  purity  of  drug  products  is  in  the  hands 
of  the  State  board  of  health  the  tendency  has  been  to  discourage 
rather  than  encourage  adequate  and  satisfactory  control  of  all  medi- 
cal supplies. 

Some  indication  of  the  nature  and  variability  of  the  products  sold 
as  medicine  may  be  had  from  a  comparative  study  of  Hygienic  Labo- 
ratory bulletins  embodying  in  the  form  of  annual  compilations  a 
"  Digest  of  Comments  on  the  Pharmacopoeia  of  the  United  States  and 
on  the  National  Formulary." 

These  bulletins,  though  not  compiled  especially  for  this  purpose, 
reflect  from  year  to  year  the  available  material  regarding  published 
activities  of  food  and  drug  laboratories  so  far  as  they  relate  to  phar- 
macopceial  or  official  drugs  and  preparations,  and  the  sum  total  of  the 
reported  activities  well  indicates  the  general  trend  of  the  trade  so  far 
as  it  is  influenced  by  the  present-day  method  of  drug-law  enforce- 
ment. 

A  compilation  of  the  analytical  reports  embodied  in  previously 
published  bulletins  shows  that  out  of  a  total  of  more  than  9000 
samples  of  6  pharmacopceial  preparations  reported  on  during  the 
years  1907  to  191 1,  inclusive,  more  than  4000,  or  approximately  45 
per  cent.,  were  found  to  be  not  in  compliance  with  the  requirements 
of  the  Pharmacopoeia.  That  approximately  this  same  ratio  still 
holds  is  evidenced  by  the  available  annual  reports  of  State  boards  of 
health  and  State  f6od  and  drug  commissioners,  abstracted  in  Hy- 
gienic Laboratory  Bulletin  No.  93,  embodying  a  Digest  of  Com- 
ments on  the  Pharmacopoeia  of  the  United  States  and  on  the  National 
Formulary  for  the  calendar  year  ending  December  31,  191 2.  Among 
the  reports  reflected  in  this  bulletin  we  find  that  the  chemist  of  the 
Indiana  board  of  health  states  that  of  365  samples  of  drugs  analyzed 
156,  or  42.7  per  cent.,  were  illegal  in  that  they  did  not  comply  with  the 
standards  or  requirements.  The  food  and  drug  commissioner  of 
South  Dakota  reports  that  of  326  samples  examined  118,  or  36.3  per 
cent.,  were  not  passed,  and  in  New  Hampshire  of  421  samples  of 
drugs  examined  by  the  chemist  of  the  board  of  health  180,  or  42.8 
per  cent.,  were  not  conformable. 

Further  evidence  regarding  existing  conditions  will  be  found  in 
the  accompanying  table  showing  the  total  number  of  samples  of 


552 


Pure  Drugs  and  the  Public  Health.  { 


Am.  Jour.  Pharm. 
December,  1914. 


26  drugs  and  preparations  reported  on  during  19 12,  the  number 
that  were  rejected  or  found  to  be  illegal,  and  the  number  of  reporters 
on  each  individual  article. 

Table  Showing  Reported  Results  of  Analysis  of  Samples  of  26  Official 
Articles — A  Compilation  of  Data  Included  in  Hygienic  Laboratory 

Bulletin  No.  93. 


Alcohol  

Ammonia,  aromatic  spirit  of . . . . 

Ammonia,  water  

Asaf  cetida  

Belladonna,  tincture  of  

Camphor,  spirit  of  

Camphor,  liniment  of  

Ferric  chloride,  tincture  of  

Ferrous  iodide,  sirup  of  

Ginger,  tincture  of  

Iodine,  tincture  of  

Lard  

Lemon  extract  

Lime  water  

Linseed  oil  

Olive  oil  

Opium,  camphorated  tincture  of, 

Opium,  tincture  of  

Peppermint,  spirit  of  

Solution  of  hydrogen  dioxide.  .  . . 
Solution  of  potassium  arsenite . . . 

Sulphur  

Sweet  spirit  of  nitre  

Turpentine,  oil  of  

Vanilla  

Witch  hazel  


Total. 


Number  of 
reporters 


7 
5 
4 
10 

3 
19 

8 

7 

8 

9 
18 

8 

10 
10 
12 
13 
5 
11 

14 
13 

7 

6 
22 

8 
12 

5 


Number  of  samples 


Examined  Rejected 


98 
116 

19 

256 

14 

802 

597 
680 

549 
74 
984 
265 
252 
635 
367 
912 

9i 
252 
270 
1,026 
570 

70 
609 

639 
286 

9i 


10,524 


47 
78 
11 

200 
6 

423 

99 
219 

88 

30 
474 

53 
100 

98 
138 

69 

30 
125 
139 

90 
128 

35 
336 
132 
116 

24 


3,288 


Per  cent, 
of  samples 
rejected 


47-9 
67.2 
57-8 
78.1 
42.8 
52.7 
16.5 
32.2 
16.0 

40-5 
48.1 
20.0 
39-6 
154 
37.6 
7-5 
32.9 
49.6 

51-4 
8.7 
22.4 
50.0 

55-i 
20.6 

40.5 
26.3 


31-2 


As  an  object  lesson  this  table  is  well  worth  studying  from  various 
points  of  view.  Not  the  least  important  in  this  connection  is  the 
suggestion  that,  despite  the  apparently  large  number  of  samples 
examined,  the  present-day  method  of  enforcing  food  and  drugs  laws 
is  hopelessly  inadequate  so  far  as  offering  to  control,  even  in  a  mod- 
erate degree,  the  nature  and  purity  of  drug  products  as  they  reach 
the  consumer. 

The  limitations  imposed  by  the  present  method  of  enforcing  the 
drug  feature  of  food  and  drugs  laws  is  well  illustrated  by  a  table 
recently  published  by  L.  P.  Brown,  food  and  drug  commissioner  of 


AD4cimber,Pi9i™'}    Pure  Dru9s  and  the  Public  Health.  553 

Tennessee  (Am.  Food  J.,  1912,  v.  7,  July,  p.  9),  showing  the  number 
of  States  in  which  food  and  drugs  laws  are  actually  being  enforced, 
the  number  of  employees  in  each  State,  and  the  number  of  samples 
analyzed  in  one  year.  This  table  states  that  no  less  than  44  political 
divisions  of  the  United  States  makes  some  attempt  to  enforce  laws  of 
this  type.  The  total  number  of  employees  recorded  is  465,  an  average 
of  but  10  to  each  State.  The  total  number  of  samples  examined 
during  one  year  is  given  as  83,498,  and  from  a  study  of  several  annual 
reports  it  is  fair  to  assume  that  not  more  than  from  20  to  25  per  cent, 
of  these  samples  represent  drug  products  or  products  used  as  drugs. 

When  one  remembers  that  in  the  United  States  alone  there  are  no 
less  than  40,000  retail  drug  stores,  and  that  each  one  of  these  stores 
has  in  stock  from  1000  to  20,000  separate  articles  used  or  offered 
for  use  as  medicine,  the  futility  of  endeavoring  to  control  or  even  to 
seriously  influence  the  nature  and  purity  of  products  sold  as  medi- 
cines by  an  occasional  examination  of  one  or  more  preparations  is  at 
once  apparent. 

That  the  present-day  method  of  enforcing  food  and  drugs  laws  is 
efficient  in  some  directions  must  be  admitted,  and  the  possibilities 
in  this  line  are  well  indicated  in  the  above  table.  Given  a  product 
that  is  more  or  less  easily  examined  by  chemical  means  and  for  which 
a  reasonably  high  standard  has  been  established  by  the  Pharmaco- 
poeia, by  statute,  or  by  regulation,  little  or  no  difficulty  is  encountered 
in  materially  improving  the  conditions  under  which  such  an  article 
is  marketed,  and  thus  securing  for  the  consumer  a  reasonably  reliable 
product  if  he  will  but  exercise  ordinary  care  in  making  his  purchases 
from  reputable  dealers. 

One  instance  of  this  type  is  olive  oil,  which  up  to  a  comparatively 
few  years  ago  was  considered  to  be  among  the  most  adulterated  of 
all  commercial  products.  This  oil,  though  largely,  if  not  preponder- 
atingly,  used  as  a  food  product,  is  also  of  value  as  a  medicine  and  can 
now  be  classed  among  the  generally  pure  articles  used  for  medicinal 
purposes. 

Another  article  that  has  been  materially  improved  through  sys- 
tematic examination  and  accompanying  publicity  is  "  solution  of 
hydrogen  peroxide."  This  preparation  is  also  used  quite  exten- 
sively in  the  arts  as  a  bleaching  material,  and  formerly  it  was  quite 
common  to  find  the  comparatively  impure  and  usually  weak  technical 
product  on  sale  in  drug  stores  for  medicinal  purposes.  Improved 
methods  of  manufacture,  the  use  of  preservatives,  and  the  exercise 


554 


Pure  Drugs  and  the  Public  Health. 


{Am.  Jour.  Pharm. 
December,  1914. 


of  a  little  additional  care  in  keeping  the  preparation  have  evidently 
combined  to  change  this  preparation  from  one  that  was  considered 
to  be  uniformly  impure  to  one  that  complies  fairly  well  with  the 
spirit  though  not  the  exact  letter  of  the  present  pharmacopceial  re- 
quirements. Disregarding  the  frequent  presence  of  a  preservative, 
only  8.7  per  cent,  of  the  preparations  examined  were  found  to  be 
deficient  in  strength  or  contaminated.  This  figure,  when  one  con- 
siders the  unstable  nature  of  the  product,  compares  very  favorably, 
indeed,  with  the  low  percentage  (7.5  per  cent,  of  samples  of  olive 
oil  rejected  during  the  same  period). 

Oil  of  turpentine  is  another  product  that  is  rapidly  being  im- 
proved, and  the  economically  closely  related  linseed  oil,  while  still 
above  the  general  average  for  all  of  the  products  reported  on  during 
19 1 2,  also  evidences  a  marked  improvement  over  previously  reported 
conditions.  These  two  products  are  very  widely  used  for  technical 
purposes  and  occupy  rather  an  anomalous  position  as  drugs.  The 
frequency  with  which  they  are  now  found  to  be  of  inferior  quality 
is  no  doubt  due  to  the  fact  that  little  or  no  attempt  has  as  yet  been 
made  to  regulate  their  identity  or  purity  for  technical  purposes,  and 
because  of  the  much  lower  price  of  the  impure  technical  products  they 
are  very  frequently  sold  in  place  of  the  official,  or  pharmacopceial, 
articles  for  medicinal  use. 

The  opposite  of  these  rather  promising  conditions  is  shown  in 
connection  with  asafcetida,  a  drug  product  of  somewhat  uncertain 
value  that  is,  nevertheless,  used  quite  extensively,  largely  perhaps 
because  of  its  penetrating  odor  and  disagreeable  taste.  The  pharma- 
copceial requirements  for  this  drug  are  unnecessarily  high  and  the 
chemical  tests  for  identity  and  purity  quite  inadequate.  It  is,  there- 
fore, not  at  all  surprising  to  learn  that  more  than  78  per  cent,  of  the 
samples  of  asafcetida  examined  did  not  comply  with  the  require- 
ments of  the  Pharmacopoeia. 

This  drug  is,  however,  but  one  of  a  number  of  articles  that  are  of 
uncertain  medicinal  value,  are  difficult  to  control  from  a  chemical 
point  of  view,  and  are  more  frequently  found  to  be  below  standard 
than  above.  This  one  fact,  that  there  are  hundreds  of  more  or  less 
widely  used  drugs  for  which  we  have  little  or  no  data  on  which  to 
base  a  chemical  control  of  the  finished  preparation,  serves  to  further 
illustrate  the  difficulty  of  exercising  any  adequate  control  of  medi- 
cinal preparations  through  a  city,  State,  or  Federal  laboratory. 

That  some  form  of  control  is  essential  is  evidenced  by  the  head 


Am.  Jour.  Pharm. 
December,  1914. 


}    Pure  Drugs  and  the  Public  Health.  555 


of  one  of  the  leading  drug  houses  in  England,  who  is  reported  as  say- 
ing that  the  thousands  of  samples  of  crude  drugs  examined  annually 
in  his  laboratories  yield  abundant  evidence  to  show  that  constant 
and  efficient  control  is  necessary  if  the  purity  of  medicinal  products 
is  to  be  maintained  and  progress  achieved  on  the  lines  of  modern 
science. 

The  reports  of  the  several  officials  intrusted  with  the  enforcement 
of  laws  relating  to  the  production  and  sale  of  drugs  have  emphasized 
time  and  again  that  much  of  the  material  that  is  now  being  sold  as 
medicine  in  this  country  is  either  directly  harmful  or  absolutely 
useless,  and  that  from  a  public-health  point  of  view  considerable 
progress  is  necessary  before  the  consumer  is  as  adequately  safe- 
guarded as  he  should  be. 

It  is  generally  recognized  that  once  a  seal  is  broken,  a  package 
opened,  or  a  cork  drawn,  the  manufacturer  can  no  longer  be  held 
responsible  for  the  content  of  the  package,  and,  quite  irrespective  of 
the  nature  of  the  medicine,  the  pharmacist  in  dispensing  a  portion 
of  an  original  package  assumes  all  responsibility  for  the  nature  and 
purity  of  the  article. 

That  this  responsibility  of  the  pharmacist  is  as  yet  not  appre- 
ciated and  that  much  progress  must  be  made  in  the  enforcement  of 
existing  laws  before  the  public  is  as  adequately  protected  as  it  should 
be,  or  has  a  right  to  expect,  is  evidenced  by  the  shortcomings  of  the 
pharmaceutical  preparations  included  in  the  table  referred  to  above, 
particularly  those  preparations  usually  made  on  a  comparatively 
small  scale  in  the  retail  drug  store.  From  the  point  of  view  of  State 
or  national  officials,  these  preparations  offer  the  most  serious  diffi- 
culties in  the  way  of  control,  through  the  intervention  of  Federal  or 
State  laboratories,  and  yet  they  are  of  considerable  importance  from 
a  medical  point  of  view  in  that  they  include  some  of  the  most  widely 
used  medicines  we  now  have.  It  has  been  well  said  that  medicine, 
particularly  the  use  of  medicines,  as  a  science  can  make  little  or  no 
progress  until  physicians  know  more  of  the  nature  and  composition 
of  the  articles  they  use  as  medicines  and  of  the  action  or  influence 
of  these  articles  on  the  healthy  as  well  as  the  diseased  organisms. 

How  little  actual  reliance  can  be  put  in  the  average  drug  prepara- 
tion at  the  present  time  will  be  appreciated  when  we  learn  that  fully 
50  per  cent,  of  such  widely  used  articles  as  aromatic  spirit  of  am- 
monia, spirit  of  camphor,  tincture  of  iodine,  tincture  of  opium,  spirit 


556 


Pure  Drugs  and  the  Public  Health. 


Am.  Jour.  Pharm. 
December,  1914. 


of  peppermint,  and  spirit  of  nitrous  ether  have  been  found  to  be 
adulterated  or  below  standard. 

Some  additional  argument  for  more  adequate  control  of  the  iden- 
tity, purity,  and  strength  of  materials  used  as  medicine  is  offered  by 
the  table  including  a  compilation  of  data  showing  the  variability  of 
well-known  and  widely  used  drugs  which  can,  in  a  measure  at  least, 
be  controlled  by  assay  and  analysis.  Preparations  of  these  drugs, 
on  assay,  are  less  frequently  found  to  be  above  than  below  standard, 
and  even  a  standardized  preparation  is  far  from  being  perma- 
nently so. 

Table  Showing  Variations  in  the  Active  Principles  of  Drugs  Reported 
During  the  Calendar  Year  Ending  December  31,  1912. 

[A  compilation  of  data  included  in  Hygienic  Laboratory  Bulletin  No.  pj.] 


Num- 

Num- 

Mini- 

Maxi- 

ber of 

ber  of 

mum 

mum 

U.  S.  P.  requirements. 

re- 

sam- 

per 

per 

porters 

ples. 

cent. 

cent. 

Belladonna  leaves. . 

S 

144 

0.175 

0.563 

0.3  per  cent,  mydriatic  alkaloids. 

Belladonna  root .  .  . 

6 

US 

.11 

.780 

0.45  per  cent,  mydriatic  alkaloids. 

3 

41 

3.720 

5.16 

3.5  per  cent,  alkaloidal  principles. 

Hydrastis  

8 

114 

2.3 

4-85 

2.5  per  cent,  hydrastine. 

Hyoscyamus  

4 

120 

.043 

.234 

0.08  per  cent,  mydriatic  alkaloids. 

10 

253 

1.24 

2.75 

1.75  per  cent,  ipecac  alkaloids. 

6 

173 

3.67 

21.76 

7  per  cent,  total  resin. 

Stramonium  

4 

127 

.14 

.470 

0.25  per  cent,  mydriatic  alkaloids. 

As  is  well  known,  all  pharmaceutical  preparations  and  many 
drugs  and  chemicals  deteriorate  on  keeping,  and  this  deterioration 
is  not  so  much  dependent  on  time  alone  as  a  number  of  accompany- 
ing factors,  as  light,  heat,  atmospheric  conditions,  and  the  general 
lack  of  care  or  technical  knowledge  in  storing  the  various  substances. 
All  in  all,  it  is  safe  to  assert  that  no  matter  how  excellent  a  drug  or 
preparation  may  be  when  it  leaves  the  producer  there  are  many 
possibilities  for  it  to  become  worthless,  if  not  positively  dangerous, 
through  carelessness  or  neglect  before  it  reaches  the  consumer. 

The  general  subject  of  changes  produced  in  a  drug  because  of  de- 
terioration due  to  improper  keeping  has  received  altogether  too  little 
attention  and  it  is  not  generally  recognized  that  many  of  the  formerly 
well  known  drugs  have  probably  been  discredited  because  of  their 
failure  to  accomplish  the  object  for  which  they  were  administered, 
a  failure  perhaps  largely  due  to  some  form  of  contamination  or  to 
decomposition  not  recognized  by  the  dispenser. 

In  addition  to  the  changes  in  drugs  that  may  be  produced  by  heat, 


Am.  Jour.  Pharm.  ) 
December,  1914.  j 


Pure  Drugs  and  the  Public  Health. 


557 


by  the  constituents  of  the  air,  by  ferments,  or  by  microorganisms, 
some  recent  observations  by  Neuberg,  of  Berlin,  suggest  that  nearly 
all  types  of  organic  compounds  acquire  a  pronounced  photosensitive- 
ness  when  they  are  mixed  with  inorganic  compounds.  Iron  salts,  it  is 
said,  provoke  such  changes  most  strikingly,  and  it  is  quite  possible 
that  otherwise  innocuous  materials  may  thus  be  converted,  in  part  at 
least,  into  decidedly  harmful  compounds. 

In  addition  to  this  possible  deterioration  of  medicaments,  which 
can  be  averted,  to  a  considerable  degree  at  least,  by  constant  care  and 
watchfulness,  there  are  a  number  of  other  factors  that  should  be 
taken  into  consideration  in  connection  with  the  dispensing  of  medi- 
cines to  the  consumer.  Not  the  least  important  of  these  several 
factors  is  the  accuracy  and  also  the  sensitiveness  of  scales,  weights 
and  measures.  On  page  43  of  Hygienic  Laboratory  Bulletin  No.  93 
will  be  found  several  references  that  bear  out  this  assertion.  One 
observer  found  that  not  one  of  36  graduates  examined  was  correct. 
Some  were  better  than  others,  but  all  were  bad.  In  the  State  of 
Kansas  nearly  one-half  of  the  prescription  weights  examined  were 
condemned,  and  of  the  718  prescription  scales  examined  195  were 
found  to  be  unfit  for  use. 

The  inability  or  unwillingness  of  retail  druggists  to  assume  proper 
responsibility  is  further  evidenced  by  the  recommendation  of  one 
man  to  use  ready-made  tablets  in  place  of  weighing  out  small  quan- 
tities of  potent  drugs.  The  fallacy  of  this  advice  has  more  latterly 
been  emphasized  by  the  fact  that  compressed  as  well  as  other  tablets, 
even  under  most  favorable  conditions,  may  vary  from  10  to  30  per 
cent,  from  the  quantities  claimed.  Under  conditions  not  so  favor- 
able even  greater  variations  have  been  observed,  and  in  cases  where 
tablets  have  been  made  to  sell  at  inordinately  low  prices  it  has  been 
found  that  expensive  chemicals  were  present  only  in  traces  sufficient 
to  give  qualitative  tests. 

In  conclusion  it  may  be  reiterated  that  the  more  evident  short- 
coming in  the  present-day  enforcement  of  pure-drugs  laws  is  the 
general  failure  to  properly  place  the  responsibility  for  the  nature, 
kind,  and  purity  of  the  medicines  supplied  to  the  consumer  where  it 
belongs.  This  shortcoming  is  being  corrected,  to  some  extent  at 
least,  by  recently  enacted  laws  to  regulate  the  practice  of  pharmacy 
by  placing  the  responsibility  squarely  on  the  person  dispensing  the 
drug. 

The  proper  enforcement  of  laws  designed  to  regulate  the  practice 


558 


Progress  in  Pharmacy. 


(  Am.  Jour.  Pharm. 
{   December,  1914. 


of  pharmacy  in  conjunction  with  pure-drugs  laws  should  relieve  phy- 
sicians and  the  public  of  any  doubt  as  to  the  composition,  purity, 
quality,  and  strength  of  all  drugs  and  medicinal  preparations  used  in 
the  treatment  of  disease.  As  these  laws  are  enforced  at  the  present 
time  it  is  plainly  evident  that  the  methods  of  control  are  inadequate 
and  do  not  serve  to  safeguard  public  health  as  well  as  they  could 
or  should. 

Boards  of  health  and  other  State  and  Federal  officials  intrusted 
with  the  enforcement  of  these  laws  should  endeavor  to  call  attention 
to  the  desirability  of  having  druggists  exercise  a  close  scrutiny  of 
the  drugs  and  preparations  included  in  their  stock,  to  keep  drugs, 
chemicals,  and  preparations  in  suitable  containers,  to  throw  away  old 
or  useless  material,  and  to  see  that  scales,  weights,  and  measures  are 
reliable  and  accurate  under  the  conditions  imposed  upon  them. 

Some  eltort  should  also  be  made  to  see  that  drug  stores  are 
equipped  with  the  necessary  analytical  apparatus  with  which  to 
analyze  or  examine  all  supplies  and  thus  assist  in  maintaining  a 
more  efficient  control  of  the  articles  sold  as  medicine. 

Consistent  and  efficient  control  of  the  identity,  purity,  and  strength 
of  all  drugs  and  preparations  as  furnished  the  consumer  would  make 
for  progress  in  the  science  of  medicine  and  should  prove  to  be  an 
important  factor  in  promoting  public  health. 


PROGRESS  IN  PHARMACY. 

A  Quarterly  Review  of  Some  of  the  More  Interesting  Litera- 
ture Relating  to  Pharmacy  and  Materia  Medica. 

By  M.  I.  Wilbert,  Washington,  D.  C. 

The  changes  in  values  of  medicinal  products  of  all  kinds  con- 
tinue to  attract  general  attention  in  the  drug  trade.  Stocks  of  a 
number  of  chemicals,  as  well  as  many  of  the  foreign  botanical  drugs, 
have  been  practically  exhausted,  and  the  prices  asked  for  these  sub- 
stances remain  high.  In  connection  with  many  other  drugs,  prices 
have  decreased  to  some  extent,  and  market  conditions  generally  are 
now  fairly  well  fixed.  The  values  of  opium  and  its  alkaloids  re- 
main high,  as  do  prices  for  nearly  all  drugs  and  chemicals  of 
German  or  of  Austrian  origin.  Prices  for  mercurials  of  all  kinds, 
Russian  paraffin  oil,  thymol,  phenol  and  phenol  products  generally 


Ain.  Jour.  Pharm. ) 
December,  1914.  j 


Progress  in  Pharmacy. 


559 


are  unusually  high,  and,  because  of  the  scarcity  of  these  products, 
still  have  an  upward  tendency. 

In  Great  Britain  the  war  is  bringing  about  a  peculiar  condition 
of  affairs  which  may  ultimately  have  a  far-reaching,  disturbing  in- 
fluence on  patent  law  enforcement.  A  recent  report  (Pharm.  J., 
1914,  vol.  93,  p.  569)  states  that  the  Board  of  Trade  has  granted  the 
application  of  Mr.  S.  Wellcome  for  a  license  to  manufacture  and 
sell  in  Great  Britain  the  drug  salvarsan,  or  "  606."  The  registra- 
tion of  the  trade-mark  has  been  suspended  for  the  time  being,  and  it 
is  proposed  that  patents  for  other  chemicals  of  German  origin  not 
now  worked  in  Great  Britain  will  also  be  suspended. 

The  New  British  Pharmacopoeia  was  placed  on  exhibition  for 
review  in  London  on  October  1,  and  will  be  available  to  the  book 
trade  on  December  31,  1914.  In  general  appearance  the  new  Pharma- 
copoeia closely  resembles  the  British  Pharmacopoeia  now  official, 
the  size  of  the  two  books  being  approximately  the  same,  despite  the 
67  additional  pages  in  the  new  pharmacopoeia,  the  discrepancy  be- 
ing accounted  for  by  the  use  of  somewhat  thinner  paper.  The 
general  impression  imparted  by  the  printed  page  is  that  the  type  and 
arrangement  of  the  material  is  practically  the  same. 

The  several  British  pharmaceutical  journals  have  presented  elab- 
orate reviews  of  the  Pharmacopoeia,  and  one  wholesale  house, 
Messrs.  Southall  Bros.  &  Barclay,  Ltd.,  of  Birmingham,  has  dis- 
tributed a  pamphlet,  of  24  pages  of  comments  on  the  new  Pharma- 
copoeia, so  that  the  available  literature  on  the  book  is  already  quite 
extensive. 

From  the  reviews  which  have  appeared  in  the  several  journals  it 
would  appear  that  the  deletions  from  the  British  Pharmacopoeia  are 
chiefly  of  drugs  and  preparations,  while  the  additions  are  mostly 
long  overdue  and  include  25  chemicals,  24  galenical  preparations, 
and  3  crude  drugs. 

The  alterations  in  strength  are  of  considerable  moment  and  are 
being  actively  discussed  in  British  pharmaceutical  journals.  The 
provisions  of  the  Brussels  Conference  Protocol  have  generally  been 
followed,  special  attention  being  directed  to  the  exceptions  made. 
The  proposed  international  drop  counter  is  recognized,  the  drop- 
ping device  being  described. 

Metric  weights  and  measures  only  are  to  be  used  in  making  or 
testing  official  products ;  the  term  "  mil  "  is  recognized  as  a  short 


560  Progress  in  Pharmacy.  {A?e'CeSrf^" 

official  designation  to  be  used  in  place  of  the  more  cumbersome  cubic 
centimetre.  Imperial  weights  and  measure  appear  only  in  connec- 
tion with  the  doses. 

The  Latin  nomenclature  employed  in  the  Ph.  Brit.  V.  has  much 
in  common  with  that  employed  in  our  own  Pharmacopoeia  of  the 
United  States,  and  a  table  of  abbreviations  of  Latin  names  of  official 
drugs  and  preparations  appears  in  the  index.  This  has  been  some- 
what roughly  handled  by  the  British  reviewers. 

An  editorial  (Chetn.  and  Drug.,  1914,  vol.  85,  p.  480)  says:  "  It 
is  hoped  that  the  abbreviations  included  in  the  Ph.  Brit.  V.  will 
never  be  put  forward  as  legally  binding.  They  do  not  appear  to  be 
at  present,  but  the  list  should  not  go  unnoticed ;  many  of  the  abbrevia- 
tions are  horrible." 

Considerable  attention  has  been  devoted  to  the  lead  and  arsenic 
limits  in  a  number  of  chemical  substances.  Tables  reproduced  in 
the  British  pharmaceutical  journals  show  that  limits  have  been  fixed 
for  a  total  of  nearly  one  hundred  official  substances. 

The  number  of  crude  drugs  and  their  preparations  which  are 
required  to  be  standardized  has  been  increased,  and  the  methods  of 
assay  have  been  brought  up  to  date. 

From  the  available  comments  it .  would  appear  that  the  phar- 
macists of  Great  Britain  are  still  somewhat  dissatisfied  with  the 
method  of  revising  the  Pharmacopoeia,  but  that  the  book,  despite 
its  many  shortcomings,  is  nevertheless  a  great  improvement  over  its 
immediate  predecessor. 

The  publication  of  the  British  Pharmacopoeia  has  again  revived 
interest  in  Great  Britain  in  the  subject  of  local  pharmacopoeias.  In 
a  recent  discussion  of  the  subject  (Pharm.  J.,  1914,  vol.  93,  p.  550)  it 
is  pointed  out  that  booklets  of  this  nature  are  intended  for  per- 
manent use  and  that  there  is  no  reason  why  they  should  not  be 
fashioned  after  a  good  model  so  as  to  make  them  not  alone  useful 
but  also  attractive  to  medical  practitioners  for  whom  they  are  in- 
tended. 

In  our  country  the  failure  to  enact  the  Harrison  bill  into  law  be- 
fore the  adjournment  of  the  second  session  of  the  sixty-third  Con- 
gress was  rather  widely  deplored.  Despite  the  opposition  that  has 
been  manifested  at  times,  it  is  generally  recognized  that  the  Harrison 
bill  is  in  no  way  a  regulatory  measure,  but  that  it  is  likely  to  be  of 
considerable  value  in  this  respect  because  of  its  being  designed  to  fur- 


Am.  Jour.  Pharm.  ) 
December,  1914.  j 


Progress  in  Pharmacy. 


nish  the  information  necessary  to  make  State  and  other  local  regula- 
tory measures  operative.  The  text  of  the  bill  as  finally  agreed  upon  in 
the  Conference  Committee  is  acceptable  to  physicians  and  phar- 
macists generally,  though  many  believe  that  it  is  unnecessarily  com- 
prehensive and  will  entail  a  greater  expenditure  of  time  and  money 
to  enforce  than  is  necessary  to  attain  the  objects  aimed  at.  In  the 
event  that  the  Conference  Report  is  agreed  to  by  the  Senate  and  the 
bill  is  signed  by  the  President,  the  new  law  will  become  operative 
on  March  I,  1915. 

Proprietary  Remedies. — The  report  of  the  Select  Committee  of 
the  House  of  Commons  on  Patent  Medicines  has  been  published  as 
a  separate  volume  of  782  pages,  and  is  now  available  through  the 
book  trade  at  6s.*  yd.,  or,  with  the  somewhat  elaborate  index,  7s.  6d. 
The  book  contains,  in  addition  to  the  findings  of  the  committee,  a 
verbatim  report  of  the  evidence  of  42  witnesses  who  appeared  be- 
fore the  committee  at  the  33  public  sittings  held  from  May  12, 
1913,  to  June  12,  1914.  One  of  the  abuses  commented  on  by  the 
Select  Committee  is  the  fact  that  the  government,  in  a  way,  is  a 
party  to  fraudulent  practices  because  of  the  collecting  of  a  stamp 
duty  on  "  patent  "  medicines  or  secret  nostrums,  which  stamp  carries 
with  it  at  least  the  suggestion  of  recognition  or  endorsement  by  the 
government. 

In  this  connection  pharmacists  in  this  country  are  to  be  com- 
mended for  their  activity  in  opposing  the  imposition  of  a  stamp  tax  on 
patent  medicines.  Many  medical  practitioners  and  pharmacists  feel 
that  such  a  tax  would,  in  a  way,  be  an  endorsement  of  these  prod- 
ucts and  would  give  them  a  standing  not  at  all  in  keeping  with  our 
present-day  knowledge  regarding  the  possibilities  and  limitations  of 
drugs  and  medicines. 

Roemer,  John,  in  a  general  discussion  of  the  patent-medicine 
problem,  expresses  the  opinion  that  pernicious  nostrums  can  be 
consistently  divided  into  six  classes  : 

1.  Those  that  bear  false  statements. 

2.  Those  whose  claims  for  medicinal  virtue  are  exaggerated. 

3.  Those  that  contain  narcotics. 

4.  Those  that  contain  alcohol  in  disguise  as  medicine. 

5.  Those  that  are  exploited  for  venereal  diseases. 

6.  Those  that  are  exploited  by  subterfuge  as  emmenagogues. 
Such  preparations  as  may  be  included  in  the  above  classification 


562 


Progress  in  Pharmacy. 


( Am.  Jour.  Pharm. 
\  December,  1914. 


can  claim  no  justifiable  right  of  existence,  much  less  sanction  or 
tolerance  for  sale  through  legitimate  pharmacy. — Proc.  New  York 
Pharm.  Assoc.,  1914,  p.  286. 

The  rapid  growth  of  pharmaceutical  manufacture  in  this  country 
is  commented  on  in  an  article  entitled  "  Drug  Intoxication,"  pub- 
lished in  Public  Health  Reports  (October  16,  1914,  vol.  29,  p.  2767), 
and  the  suggestion  is  made  that  the  steady  increase  in  the  death-rate 
from  so-called  degenerative  diseases  may  be  in  a  measure  accounted 
for  by  the  injuries  brought  about  by  the  promiscuous  use  or  abuse 
of  actively  poisonous  drugs. 

Bromide  Rash. — Weiss,  Ludwig,  reports  an  unusual  case  of 
bromoderma  of  the  leg  in  a  female,  aged  24,  who  had  taken  potassium 
bromide  for  a  number  of  years. — /.  Am.  M.  Assoc.,  1914,  vol.  63, 

PP-  635-639- 

Suicides  and  Newspaper  Publicity.  {Anon.) — The  probable  in- 
fluence of  newspaper  publicity  of  details  with  regard  to  the  nature 
and  kind  of  substances  used  in  connection  with  cases  of  poisoning 
is  well  shown  by  a  compilation  from  the  reports  of  the  coroner  of 
St.  Louis  for  the  years  1910  to  1914,  inclusive.  The  figures  given 
suggest  the  desirability  of  telling  the  truth  in  regard  to  the  action 
of  corrosive  poisons  and  the  need  for  refraining  from  even  an  in- 
timation that  the  use  of  any  one  poison  or  substance  may  lead  to  a 
sure  and  painless  death. — /.  Am.  M.  Assoc.,  1914,  vol.  63,  pp.  660, 
601. 

Poisons  and  Habit-forming  Drugs. — Progress  in  the  way  of  legis- 
lation to  restrict  the  sale  and  use  of  poisons  and  habit-forming  drugs 
is  reviewed  in  the  introduction  to  a  second  supplement  to  Public 
Health  Bulletin  No.  56.  This  supplement,  the  introduction  to  which 
appears  in  Public  Health  Reports  for  November  13,  1914,  includes  a 
digest  of  laws  and  regulations  relating  to  the  possession,  use,  sale, 
and  manufacture  of  poisons  and  habit-forming  drugs  enacted  dur- 
ing 1913  and  1914.  The  compilation  should  be  of  considerable  in- 
terest to  pharmacists  in  all  parts  of  the  United  States  who  may  be 
called  upon  to  endorse  or  to  oppose  prospective  legislation  along  this 
line. 

Solid  Alcohol. — The  use  of  solidified  alcohol  for  rubbing  and  for 
general  disinfection  purposes  is  meeting  with  increasing  popularity. 
The  production  of  alcohol  in  solid  form  would  appear  to  offer  a 


Am.  Jour.  Pharm.  ) 
December,  1914.  / 


Progress  in  Pharmacy. 


563 


possibility  for  denaturing  the  product  in  such  a  way  as  to  make  the 
tax-free  article  available  for  external  use  in  medicine. 

Amylum.  (Southworth,  Thomas  S.) — While  it  is  an  established 
fact  that  even  young  infants  are  prepared  to  digest  moderate  quan- 
tities of  boiled  starch,  the  indication  for  its  use  appears  to  lie  in  those 
suffering  from  disturbances  of  digestion  and  nutrition.  The  chief 
end  subserved  by  the  addition  of  starch  is  not  solely  to  nourish  the 
infant,  but  to  promote  nutrition  by  making  possible  a  more  orderly 
digestion  and  absorption  of  its  main  nutriment,  milk. — /.  Am.  M. 
Assoc.,  1914,  vol.  63,  p.  1377. 

Camphor.  (Cairis,  Valentine.) — The  comparative  toxicity  of  cam- 
phor in  different  vehicles.  In  the  undissolved  state  the  lethal  dose  of 
camphor  in  the  digestive  system  of  the  guinea-pig  is  between  0.14  and 
o.i8~Gm.  per  100  Gm.  body  weight.  In  ether-alcohol  solution  the 
toxicity  is  markedly  increased.  Dissolved  in  oil,  it  is  notably  less 
poisonous.  When  given  hypodermically,  the  toxicity  of  camphor  in 
oily  solutions  is  far  below  that  in  alcohol  and  water,  and  in  all  cases 
is  greater  than  the  effect  produced  by  oral  administration.  The 
toxicity  is  much  higher  by  peritoneal  injection  than  by  any  other  way 
of  administration;  but  by  this  method  the  oily  solution  is  still  the 
least  toxic  of  any. — /.  Pharm.  Chem.,  1914,  vol.  10,  p.  224 ;  Pharm.  J., 
1914,  vol.  93,  p.  457. 

Cottonroot  Bark. — Power  and  Browning  report  a  chemical 
examination  of  cottonroot  bark.  No  alkaloid  is  contained  in  the 
bark,  and  no  evidence  could  be  obtained  of  the  presence  of  tannin.— 
Pharm.  J.,  1914,  vol.  93,  p.  423. 

Ergot.  (Rosenbloom  and  Schildecker.) — The  successful  isola- 
tion of  ergotin  in  crystals  from  certain  organs  in  a  case  of  acute  ergot 
poisoning. — /.  Am.  M.  Assoc.,  1914,  vol.  63,  pp.  1203,  1204. 

Ipecac.  (Hesse,  O.) — Ipecamine  and  hydroipecamine,  two  new 
alkaloids,  were  found  in  the  course  of  an  investigation  of  the  alka- 
loidal  constituents  of  ipecacuanha. — Liebig's  Annalen,  1914,  vol.  403, 
p.  1 ;  Pharm.  J.,  1914,  vol.  93,  p.  425. 

Mercuric  Benzoate.  (Rupp  and  Hermann.) — Mercuric  benzoate, 
which  is  official  in  the  French  Pharmacopoeia,  has  been  recom- 
mended as  the  most  suitable  salt  for  hypodermic  injection.  Since 
it  is  a  normal  salt  it  is  not  apparent  why  it  should  be  less  ionized  in 
solution  than  any  other  mercuric  salt. — Arch.  d.  Pharm.,  vol.  252,  No. 
3 ;  Pharm.  J.,  1914,  vol.  93,  p.  323. 


564 


Progress  in  Pharmacy. 


{Am.  Jour.  Pharm. 
December,  1914. 


•  The  Prognosis  in  Morphine  Addiction.  (Konig,  H.) — The  prog- 
nosis naturally  varies  according  as  the  addiction  was  acquired  in 
connection  with  <a  chronic  painful  affection,  such  as  tabes,  neuralgia, 
or  peritoneal  adhesions,  or  with  single  periods  of  pain,  such  as  gall- 
stone colic,  or  in  connection  with  periods  of  melancholia  or  insomnia. 
Experience  with  28  cases  is  reviewed,  demonstrating  a  successful 
outcome  in  over  50  per  cent,  of  the  14  in  the  gall-stone  group.  The 
treatment  required  from  three  to  ten  months  in  these  cases. — Berl. 
klin.  W chnschr.,  vol.  51,  June  1,  No.  22;  /.  Am.  M.  Assoc.,  1914, 
vol.  63,  p.  204. 

Commercial  Papain  and  Its  Assay.  (Adams,  H.  M.) — Commercial 
papain  is  sometimes  adulterated  with  starch  or  pepsin.  The 
presence  of  starch  is  shown  by  the  addition  of  iodine  solution, 
and  the  pepsin  by  comparative  observations  on  the  digestion  of 
meat  in  a  weak  acid  and  in  a  neutral  or  alkaline  solution.  To  de- 
termine the  proteolytic  power  of  papain,  neutral  solutions  give  the 
most  satisfactory  results  with  either  meat  or  the  whites  of  eggs. — 
/.  Ind.  and  Eng.  Chem.,  19 14,  vol.  6,  pp.  669,  670. 

Acitrin. — Phenolcinchoninicacidethylester,  a  yellowish,  odorless, 
and  tasteless  powder,  melting  at  590,  only  slightly  soluble  in  organic 
solvents.  On  boiling  with  acids  or  alkalies  the  ester  is  saponified. — 
Sudd.  Apoth.-Ztg.,  1914,  vol.  54,  p.  137. 

Agar-agar  Biscuits.  (Anon.) — To  make  agar-agar  biscuits  it  is 
only  necessary  to  add  the  fine  agar-agar  to  the  flour  used  in  making 
the  biscuits.  The  amount  should  be,  if  possible,  sufficient  so  that  a 
dose  (5  grammes)  may  be  included  in  each  biscuit. — /.  Am.  M. 
Assoc.,  1914,  vol.  63,  p.  1224. 

Algocratine. — Mannich  and  Leemhuis  report  an  examination  of 
a  powder  offered  as  an  infallible  remedy  for  migraine,  neuralgia, 
grippe,  influenza,  and  other  diseases.  The  preparation  was  found  to 
consist  essentially  of  a  mixture  of  phenacetin,  50  Gm.,  caffeine,  10 
Gm.,  and  pyramidon,  40  Gm.  The  claims  made  for  the  composition 
of  the  preparation  were  found  to  be  quite  untrue. — Apoth.-Ztg.,  1914, 
vol.  29,  p.  553. 

Amphotropin. — A  combination  of  camphoric  acid  and  hexa- 
methylentetramine,  C8H14  (COOH)2  [  (CH|2)6N4]2.  A  white  crys- 
talline powder  having  an  acid  reaction,  soluble  in  10  parts  of  water 
at  room  temperature,  more  readily  soluble  in  hot  water  and  in 
alcohol. — Sudd.  Apoth.-Ztg.,  1914,  vol.  54,  p.  137. 


Am.  Jour.  Pharm. ) 
December,  1914.  J 


Progress  in  Pharmacy. 


565 


Apendicol.  (Mannich  and  Leemhuis.) — This  name  is  applied  to 
a  paraffin  oil  colored  red  and  containing  a  minute  quantity  of  fruit 
ether  as  a  flavor. — Apoth.-Ztg.,  1914,  vol.  29,  p.  672. 

Apyron.  (Anon.) — Lithium  acetylsalicylate.  Contains  96.26  per 
cent,  of  acetyl  salicylic  acid  and  3.74  per  cent,  of  lithium. — Chem. 
and  Drug.,  1914,  vol.  85,  p.  376. 

Arsylate.  (Anon.) — Dimethyl  aminotetramido-arseno-benzene. 
A  liquid  easily  absorbed  in  subcutaneous  injection.  It  is  a  substitute 
for  salvarsan. — Chem.  and  Drug.,  1914,  vol.  85,  p.  376. 

Atrinal.  (Anon.) — Atropine-sulphonic  acid,  a  new  mydriatic 
preparation  manufactured  by  the  Hoffmann-La  Roche  Company. — 
Chem.  and  Drug.,  1914,  vol.  85,  p.  376. 

Catin.  (Mannich  and  Leemhuis.) — A  preparation  marketed 
under  this  name  was,  on  examination,  found  to  consist  of  zinc  sul- 
phocarbonate. — Apoth.-Ztg.,  1914,  vol.  29,  p.  694. 

Cerephysin. — The  name  applied  to  an  extract  made  from  the 
infundibular  portion  of  the  hypophyses  of  cattle.  One  cubic  centi- 
metre of  cerephysin  corresponds  to  0.2  Gm.  of  moist  organ  sub- 
stance. It  occurs  as  a  clear  water-white  liquid  dispensed  only  in 
ampoules. — Sudd.  Apoth.-Ztg.,  1914,  vol.  54,  p.  137. 

Chineonal.  (Erdt,  V.)- — Fatal  poisoning  in  a  child  of  three  who 
swallowed  nine  tablets  of  chineonal  tablets  during  the  day.  The  child 
had  taken  in  the  tablets  the  equivalent  of  0.648  gramme  of  veronal  in 
six  or  eight  hours. — Munch,  med.  W chnschr.,  vol.  51,  August  25, 
No.  34;  /.  Am.  M.  Assoc.,  1914,  vol.  63,  p.  1431. 

Collar got.  (Cromwell,  Andrew  J.) — Collargol  in  pyelography, 
with  a  report  of  an  interesting  case  and  a  note  on  a  number  of  ex- 
periments on  dogs.  From  the  pathologic  findings  and  from  the  ex- 
perimental work  on  dogs  the  author  is  convinced  that  the  use  of 
collargol  in  pyelography  is  not  without  danger,  and  that  efforts 
should  be  made  to  secure  a  substance  less  harmful  for  this  purpose. — 
/.  Am.  M.  Assoc.,  1914,  vol.  63,  pp.  1 387-1 389. 

Digimorval.  (Anon.)—  Each  tablet  is  said  to  contain  0.005  Gm. 
of  morphine  and  0.05  Gm.  of  powdered  digitalis  and  3  drops  of 
mentholvalerianate. — Sildd.  Apoth.-Ztg.,  19 14,  vol.  54,  p.  153. 

Friedmann  Remedy. — Additional  contributions  on  the  Friedmann 
remedy  emphasize  previous  reports  that  the  remedy  has  not  proved 
successful  either  in  simple  cases  of  tuberculosis,  in  surgical  cases,  or 
in  lupus. — Therap.  Monatsh.,  1914,  vol.  28,  p.  630. 


S<56 


Progress  in  Pharmacy. 


f  Am.  Jour.  Pharm. 
\  December,  1914. 


Friedmann  Remedy.  (Editorial.) — In  the  Public  Health  Service 
report  on  the  Friedmann  remedy  the  investigators  summarize  their 
conclusions  in  the  following  succinct  statements :  "  The  claim  of  Dr. 
F.  F.  Friedmann  to  have  originated  a  specific  cure  for  tuberculosis 
is  not  substantiated  by  our  investigation.  The  claim  of  Dr.  F.  F. 
Friedmann  that  the  inoculation  of  persons  and  animals  with  his 
organisms  is  without  harmful  properties  is  disproved." — /.  Am.  M. 
Assoc.,  1914,  vol.  63,  pp.  1690,  1691. 

Lacpinin.  (Kiihl,  Hugo.) — This  article  was  found  to  be  an 
emulsion  of  pine  'needle  oil  containing  20  per  cent,  of  the  oil  of 
Abitis  sibiricce. — Sudd.  Apoth.-Ztg.,  19 14,  vol.  54,  p.  488. 

Neohexal. — A  combination  of  hexamethylenetetramine  and  sul- 
pho-salicylic  acid  which  has  been  recommended  as  an  antiseptic 
for  the  urinary  tract. — Therap.  Monatsh.,  1914,  vol.  28,  p.  629. 

Orthoform.  (McCleave,  T.  C.) — Idiosyncrasy  to  orthoform. 
The  experience  reported  indicates  that  it  cannot  be  used  with  im- 
punity in  all  persons,  even  in  very  small  doses. — /.  Am.  M.  Assoc., 
1914,  vol.  63,  p.  1666. 

Parakodin. — A  proprietary  name  for  di-hydro-codeine  which  has 
been  recommended  as  an  expectorant,  a  sedative,  and  a  substitute 
for  morphine.  Among  the  secondary  effects  observed  are  decrease 
in  appetite,  retching  and  nausea.  It  is  given  in  doses  of  from  0.02  to 
0.05  Gm. — Therap.  Monatsh.,  1914,  vol.  28,  p.  630. 

Phenoval. — A  sedative  and  hypnotic  which  has  been  recommended 
for  the  reduction  of  pain  and  for  nervous  patients ;  also  as  a  narcotic. 
— Therap.  Monatsh.,  1914,  vol.  28,  p.  629. 

Rhodoform.  (Anon.) — A  sulphocyanate  of  hexamethylene-tetra- 
mine.  It  is  a  white,  odorless  powder,  recommended  as  an  antiseptic 
for  use  in  the  treatment  of  diseases  of  the  mouth  and  larynx. — Chem. 
and  Drug.,  1914,  vol.  85,  p.  376. 

Thiophysein.  (Anon.) — A  new  organic  iodine  preparation,  be- 
ing an  addition-product  of  ethyl-thio-urea  and  ethyl  iodide.  It  is 
easily  soluble  in  water,  and  is,  therefore,  a  suitable  form  for  the 
administration  of  iodine  in  organic  combination. — Chem.  and  Drug., 
1914,  vol.  85,  p.  376. 


Am.  Jour.  Pharm.  \ 
December,  1914.  J 


Current  Literature. 


567 


CURRENT  LITERATURE. 
Digitalis. 

The  second  instalment  of  Dr.  Robert  H.  Hatcher's  two-part 
paper  on  digitalis  is  presented  in  the  October  number  of  the  Drug- 
gists Circular,  and,  like  its  precursor,  is  both  interesting  and  in- 
structive. In  it  he  deals  altogether  with  the  pharmacology  of  this 
much-experimented-with  and  much-discussed  drug,  and  closes  with 
an  excellent  summary  which  embraces  the  conclusions  arrived  at  in 
both  papers.  An  adequate  abstract  of  these  papers  is  almost  im- 
possible. Physicians  and  pharmacists  should  really  read  and  study 
the  original  papers. 

The  author  recapitulates  as  follows :  "  Digitalis  of  the  'first  year's 
growth  is  probably  as  active  as  that  of  the  second,  the  cultivated  as 
active  as  the  wild-grown. 

"  The  most  active  digitalis  is  not  necessarily  the  best ;  the  best  be- 
ing that  which  possesses  a  maximum  of  therapeutic  actions  with  a 
minimum  of  side  actions,  such  as  the  nauseant  and  emetic.  It  is  not 
known  at  what  period  digitalis  possesses  this  advantage. 

"  The  drying  and  storage  of  digitalis  require  no  exceptional  con- 
ditions. Like  all  vegetable  drugs,  it  should  be  selected  carefully, 
dried  properly,  and  stored  so  that  it  will  not  become  mouldy.  It 
will  then  keep  indefinitely. 

"  Pharmaceutical  preparations  of  digitalis  which  contain  at  least 
60  per  cent,  of  alcohol  in  the  finished  product  will  keep  almost  in- 
definitely under  all  ordinary  conditions  of  storage,  where  the  con- 
tainers are  kept  securely  corked  and  away  from  sunlight. 

"  At  least  two  principles — digitoxin  (or  crystalline  digitalin  of 
Nativelle),  and  true  digitalin  of  Schmiedeberg,  or  of  Kiliani — are 
obtained  from  digitalis  leaf,  and  it  is  possible  that  a  third  thera- 
peutically active  substance,  digitalein,  may  be  so  obtained  in  fairly 
pure  form,  but  not  absolutely  pure. 

"  It  is  not  absolutely  certain  that  these  exist  preformed  in  the 
leaf. 

"  There  is  no  digitalis  principle  or  preparation,  pharmacopceial 
or  proprietary,  which  has  the  advantage  of  digitalis  without  certain 
undesired  effects,  such  as  nausea  and  vomiting.  Cumulation,  so- 
called,  also  pertains  to  all  digitalis  principles,  as,  indeed,  it  does  to 
all  drugs. 


568    "  Current  Literature.  | Am-  'w.  ite 

^  \   December,  1914. 

"  Any  pharmacist  can  obtain  digitalis  without  paying  an  ex- 
orbitant price  for  it,  and  he  can  make  a  tincture  equal  to  the  best, 
and  quite  as  useful  therapeutically  as  any  of  the  proprietary  prep- 
arations. 

"  The  tincture  represents  all  of  the  activities  of  the  leaf ;  so  does 
the  infusion  when  properly  made  from  leaf  in  No.  60  powder,  and 
these  two  preparations  have  an  identical  action  in  corresponding 
doses. 

"  The  fat-free  tincture  has  no  advantages  over  the  official  tinc- 
ture. 

"  The  determination  of  the  digitoxin  content  of  the  leaf  affords 
no  index  of  the  therapeutic  or  pharmacologic  activity  of  the  drug, 
but  the  therapeutic  activity  may  vary  in  the  same  direction  as  the 
digitoxin. 

"  No  test  for  digitalis,  chemical  or  biologic,  is  satisfactory,  but 
the  one-hour  frog  method  is  probably  best  suited  to  the  general  needs 
of  the  pharmacist,  and  this  will  probably  be  admitted  to  the  ninth 
edition  of  the  United  States  Pharmacopoeia. 

"  The  dose  of  digitalis  cannot  be  expressed  in  fixed  terms,  be- 
cause it  varies  widely  with  the  frequency  of  repetition,  the  length  of 
time  during  which  it  is  intended  to  be  taken,  and  dependent  upon 
whether  the  patient  has  recently  had  similar  medication.  It  is  prob- 
ably safe  to  say  that  not  more  than  45  grains  of  the  leaf  or  a 
fluidounce  of  the  tincture  should  be  administered  to  a  patient  within 
a  period  of  one  week,  and  such  an  amount  only  under  the  immediate 
observation  of  a  trained  clinician,  and  such  an  amount  could  not  be 
given  safely  immediately  after  medication  with  digitalis  or  syner- 
gistic drugs."   The  Druggists  Circular,  October,  1914,  p.  607. 

J.  K.T. 

NEWS  ITEM 

Dr.  Frederick  B.  Power  will  retire  from  the  directorship  of  the 
Wellcome  Chemical  Research  Laboratories  on  the  first  of  December 
in  order  to  return  to  the  United  States  where,  for  family  reasons, 
he  will  make  his  future  home,  at  535  Warren  Street,  Hudson,  New 
York. 

The  high  character  of  the  research  work  carried  out  in  these 
Laboratories  under  the  immediate  direction  of  Dr.  Power  stands 
without  a  parallel  in  his  department  of  science.  It  has  been  truly 
said  that  Dr.  Power  has,  during  the  period  of  his  administration, 
inaugurated  a  new  era  in  his  field  of  research  in  England. 


/  V  ^  \ 

f     DEC  7  1914 

INDEX  M^TEHT^^ 

TO  VOLUME  86  OF  THE  AMERICAN  JOURNAL 
OF  PHARMACY.1 

AUTHORS. 

Anderson,  John  F.  The  United  States  Public  Health  Service   155 

Beringer,  George  M.  A  Note  on  the  Value  of  the  Preservatives  in  Syrup 

of  Iron  Iodide   358 

Bichloride  of  Mercury  Tablets  and  Bichloride  Legislation   313 

Bessey,  Charles  E.   The  Volatile  Nature  of  the  Toxic  Constituent  of 

Poison  Ivy    112 

Bhaduri,  Kshitibhushan.   Constituents  of  Andrographis  Paniculata   349 

The  Oil  of  Argemone  Mexicana   49 

Bradbury,  Robert  H.    Colloids  and  Crystals,  The  Two  Worlds  of  Matter.  71 

Caryl,  C.  R.,  F.  W.  Heyl,  and  J.  F.  Staley.    Standardization  of  Commercial 

Papain    542 

Chapin,  Robert  M.    The  Assay  of  Mercuric  Chloride  Tablets   1 

Crawford,  Albert  C.    Contribution  to  the  Chemistry  of  the  Pituitary 

Pressor  Compounds   291 

Cushman,  O.  E.    A  Study  of  Some  of  the  Methods  for  the  Determination 

of  Calomel  in  Calomel  Tablets   511 

Day,  W.  B.    A  Plea  for  More  Effective  Co-operation  Among  Pharmaceuti- 
cal Organizations    263 

DuMez,  A.  G.    Hyoscine  and  Scopolamine   339 

Fieselmann,  Sidney  F.   An  Assay  Process  for  Quinine  in  Tablets   54 

Gesell,  Hans.   The  Assay  of  Zinc  Stearate   120 

Gordin,  H.  M.    Notes  on  the  Estimation  of  Morphine  and  on  Lloyd's 

Reagent   461 

Hamilton,  H.  C.    U.  S.  P.  1900  Menstrua   56 

Haskell,  C.  C.    Seasonable  Variations  in  the  Resistance  .of  Guinea  Pigs 

to  Poisoning  by  Ouabain  and  Liquid  Preparations  of  Digitalis..   7 

Heyl,  F.  W.    Analyses  of  Two  Echinacea  Roots   450 

Notes  on  the  Estimation  of  Nitroglycerin   195 

C.  R.  Caryl  and  J.  F.  Staley.  Standardization  of  Commercial  Papain.  .  542 
Hilton,  S.  L.    Petrolatum  Liquidum,  U.  S.  P.  VIII  (Paraffinum  Liquidum) 

White  Mineral  Oil   360 

Hindman,  Edith.    Rhamnus  Purshiana,  Its  History,  Growth,  Methods  of 

Collection  and  Bibliography   387 

Hitchens,  A.  Parker.    Theories  Underlying  the  Use  of  Antitoxins  and 

Vaccines    198 

Holmes,  E.  M.    Sandalwood,  Oil  of   31 

Honsaker,  C.  C.    Efficiency  in  Drug  Stores   265 

Johnson  C.  W.    Rhamnus  Purshiana,  Its  History,  Growth,  Methods  of 

Collection  and  Bibliography   387 

1  Compiled  by  M.  G.  Smith. 

(569) 


C7r%  Tudcr  f  Am.  Jour.  Pharm. 

57°  maex.  -j  Dccemberj  1914> 

Kaplan,  J.  Notes  on  the  Estimation  of  Morphine  and  on  Lloyd's  Reagent.  461 
Kraemer,  Henry.    The  Influence  of  Heat  and  Chemicals  on  the  Starch 

Grain    81 

Lyon,  Vincent  B.  B.    A  Consideration  of  Autogenous  Vaccines   206 

Marden,  J.  W.    A  Study  of  Some  of  the  Methods  for  the  Determination 
of  Calomel  in  Calomel  Tablets   511 

Mayer,  Joseph  L.    Preparation  and  Analyses  of  Vleminckx's  Solution.  . .  .  355 

Mirkin,  A.    A  Ne\v  Method  for  the  Determination  of  Phenolphthalein.  ..  307 
On  the  Determination  of  Acetanilid   354 

Miiller,  S.  Bertha.    Magma  Bismuthi   11 

Newcomb,  Edwin  L.    Belladonna  and  Hyoscyamus   531 

North,  Horace.    The  Volumetric  Estimation  of  Sulphates   249 

Ostenberg,  Zeno.    Contribution  to  the  Chemistry  of  the  Pituitary  Pressor 

Compounds   291 

Pearson,  William  A.    The  Physiological  Standardization  of  the  Heart 

Tonics   61 

Pilcher,  J.  D.    Note  on  the  Solubility  of  Phenol  in  Hydrocarbons   149 

Puckner,  W.  A.    Liquid  Petrolatum  or  Russian  Mineral  Oil   322 

Reinick,  William  R.    Books  as  a  Source  of  Disease   13 

Remington,  Joseph  P.    The  Procter  Memorial.    An  Appreciation   243 

Rippetoe,  J.  R.    Applied  Pharmacognosy   114 

Rowe,  L.  W.    The  Sterilization  of  Adrenalin  Solutions   145 

Sievers,  A.  F.    Distribution  of  Alkaloids  in  the  Belladonna  Plant   97 

The  Germination  of  Belladonna  Seed   483 

Smith,  E.  E.    The  Physiological  Characteristics  of  Acetylene,  with  Respect 

to  Its  Use  in  Mining   363 

Staley,  J.  F.    Analyses  of  Two  Echinacea  Roots   450 

Notes  on  the  Estimation  of  Nitroglycerin   195 

F.  W.  Heyl,  and  C.  R.  Caryl.    Standardization  of  Commercial  Papain.  542 

Stiles,  Percy  G.  The  Vitamines :  The  Recognition  of  Essential  Con- 
stituents of  the  Diet  Hitherto  Unclassified.   Deficiency  Diseases   237 

Stockberger,  W.  W.    Medicinal  Plant  Gardens   506 

Talbot,  Henry  P.  Ehrlich's  Chemotherapy.  How  his  Logical,  Systematic 
Campaign  Against  Certain  Diseases  Has  Demonstrated  the  Value 
of  Scientific  Methods  in  Therapeutical  Problems   25 

Thum,  John  K.    Abstracts  of  Some  Papers  Read  at  the  1913  Meeting  of 

the  Pennsylvania  State  Pharmaceutical  Association   37 

Red  Gum    449 

Warren,  L.  E.    The  Detection  of  Emodin-bearing  Drugs  in  Presence  of 

Phenolphthalein    444 

Wilbert,  M.  I.    U.  S.  P.  IX  Limitations  for  the  Ash  Content  of  Drugs.  .  456 

Progress  in  Pharmacy    128,  272,  416,  558 

Pure  Drugs  and  the  Public  Health    550 

Renewed  Interest  in  Paraffin  Oil.   150 

The  Patent  Medicine  Problem   256 

The  Sale  of  Bichloride  Tablets   121 

The  65th  Annual  Session  of  the  American  Medical  Association   374 

Williams,  J.  B.    The  Estimation  of  Morphine  in  Pills,  Tablets,  etc   308 

The  Insecticidal  Value  of  Fluidextract  of  Larkspur  Seed   414 


Am.  Jour.  Pharm. )  Iwripr  C7T 

December,  1914.  J  l  nueA .  1 

SUBJECTS 

Acetanilid,  On  the  Determination  of  (Mirkin)    354 

Acetylene.    The  Physiological  Characteristics  of,  with  Respect  to  Its  Use 

in  Mining  (Smith)   363 

Acetyline    278 

Acitrin   564 

A    Afridol   278 

Agar-agar  Biscuits    564 

Alcohol,  Anhydrous.   An  Examination  of  Some  Drugs  with  Special  Refer- 
ence to  (Rippetoe)    435 

Solid   564 

Algocratine   427 

Alkaloids  in  Aqueous  Solution  and  in  the  Form  of  Galenicals,  The  Rate  of.  422 

Aloes   133 

Alypin   133,  278 

American  Chemical  Society,  Annual  Meetings  of .   275 

The  Summer  or  Fall  Meeting   418 

American  Medical  Association,  Chemical  Laboratory,  Annual  Reports  of.  .  276 

Meeting  of  the  '. . :.  275 

The  65th  Annual  Session  of  the  (Wilbert)   374 

American  Pharmaceutical  Association.   Reformed  Measures   129 

The  Sixty-second  Annual  Meeting  of  the   464 

Amphotropin    564 

Amylum   ,   563 

Andrenalin  Solutions,  The  Sterilization  of  (Rowe)   145 

Andrographis  Paniculata,  Constituents  of  (Bhaduri)   349 

Antimeningitis  Serum    427 

Antitoxin  and  Vaccines,  Theories  Underlying  the  Uses  of  (Hitchens)  ....  198 

Apendicol    565 

Apyron    565 

Argemone  Mexicana,  The  Oil  of  (Bhaduri)   49 

Argyrism   279 

Arheol    134 

Arsylate    565 

Ash  Content  of  Drugs,  Proposed  U.  S.  P.  IX  Limitations  for  the  (Wilbert)  456 

The  Examination  of  Some  Drugs  with  Special  Reference  to  (Rippe- 

.t°e)   •   435 

Aspidospermme   279 

Aspirin   279 

Assay  Process    418 

Atophan   134 

Atrinal   565 


Barbaloin,  Transformation  of,  into  Beta-barbaloin   427 

Bark,  Cotton  Root    563 

Belladonna  and  Hyoscyamus  (Newcomb)   531 

Leaves,  The  Adulteration  of...   421 

Plant,  Distribution  of  Alkaloids  in  (Sievers)   97 

Seed,  The  Germination  (Sievers)   483 

Benzoate,  Mercuric    563 

Benzoin,  The  Analytical  Characters  of   422 

Siam   140 

Bichloride  Tablets                                                                            '  427 

The  Sale  of  (Wilbert)   121 

Bill,  Anti-narcotic,  The  Harrison  273,  425 

Boy lan    273 

Books  as  a  Source  of  Disease  (Reinick)   13 


572 


Index. 


(  Am.  Jour.  Pharm. 
\  December,  1914. 


Boy lan  Law   .   426 

Bromide  Rash    562 

Calomel  Tablets,  A  Study  of  Some  of  the  Methods  for  the  Determination 

of  Calomel  in  (Marden  and  Cushman)   511 

Camphor   563 

in  Tablets  and  Pills,  The  Determination  of   428 

Carbon  Disulphide  in  Official  Pharmacy  and  Suggestion  for  its  Further 

Use,  The  Place  of   423 

Catin  .565 

Cerephysin   565 

Cereus  Grandiflorus   134 

Cerolin   428 

Chineonal    565 

Chromium  Sulphate   134 

Cinnamic  Aldehyde,  The  Stability  of  ,   423 

Cocaine    279 

Coffee,  Chemistry  of  a  Cup  of   216 

Collargol    279 

Colloids  and  Crystals,  The  Two  Worlds  of  Matter  (Bradbury)   71 

Consumption  Cure    420 

Creolin  (refers  to  Cerolin)   279 

Crotalin  •   280 

Cunila  Mariana    135 

Cusylol   135 

Cymarin  .  .  .  280,  428 

Diachylon  :   280 

Dicoma  Anomala,  Chemical  Examination  of   225 

Digest  of  Comments                                                                    131,  277,  378 

Digimorval    565 

Digipan   135 

Digitalis    567 

and  Its  Preparations   517 

Diogenal  .  135 

Diphtheria  Vaccine,  Behring's  .'   134 

Distribution  of  Alkaloids  in  the  Belladonna  Plant  (Sievers)   97 

Doses,  Pharmacopceal  :   132 

Drug  Addicts    274 

Intoxication    562 

Standards   224 

Store,  Efficiency  in  (TTjnsaker)   265 

Store  Strike   131 

Trades  Conference   130 

Users,  Pleads  for   144 

Drugs,  Absorption  of,  Studies  on   426 

Habit  Forming    562 

Pure,  and  the  Pharmacist   275 

Pure  and  the  Public  Health  (  Wilbert)  

Useful                                                                                 131,  276,  418 

Echinacea    135 

Roots,  Analyses  of  Two  (Heyl  and  Staley)   45° 

Education,  Pharmaceutical   189 

Ehrlich's  Chemotherapy.    How  his  Logical,  Systematic  Campaign  Against 
Certain  Diseases  has  Demonstrated  the  Value  of  Scientific  Methods 

in  Therapeutical  Problems  (Talbot)   25 

Eisenzucker    428 


Am.  Jour.  Pharm. ) 

December,  1914.  J 


Index. 


573 


Elarson    135 

Electrargol    428 

Emetine  Hydrochloride   136 

Emodin-bearing  Drugs,  The  Detection  of,  in  Presence  of  Phenolphthalein 

(Warren)   444 

Erepton    280 

.Ergot   136 

Ether,  Anaesthetic,  of  Commerce   424 

Extracts,  The  Examination  of  Some  Drugs  with  Special  Reference 

_   to  (Rippetoe)    435 

Eusitin    280 

Extractum  Filicis  Maris  Liquidum,  An  Improved  Method  for  the  Adminis- 
tration of   423 

Fluid  Extract  Manufacture,  Total  Extractive  as  a  Factor  in    418 

Food  and  Drug  Questions,  U.  S.  Chamber  of  Commerce  to  Study   529 

Food  and  Drugs  Law    419 

Guarantee  of   285,  287 

Formulary,  Era   277 

French  Fellowship  in  the  Philadelphia  College  of  Pharmacy,  The  Clayton.  245 

Friedmann  Institutes   133 

Remedy   281,  428 

Fucitol    136 

Galegine  Sulphate   429 

Gardens,  Medical  Plant  (Stockberger)   506 

Gaseous  Impurities  in  the  Air  of  Railway  Tunnels   481 

Gelatin  Capsules,  Formalized   185 

Gitalin    429 

Gitonin   136 

Glycerophosphates  of  Commerce,  The  Composition  of  the   423 

Glyco-Heroin,  Smith    429 

Goldenseal  an  Admirable  Crop,  Ginseng  Growers  May  Find   525 

Gossyppii  Cortex    563 

Gum,  Red  (Thum)   449 

Habit-forming  Drugs    562 

Hay  Fever,  The  Serum  Treatment  of  ,  288,  289 

Health  Service,  The  United  States  Public  (Anderson)   155 

Heart  Tonics,  The  Physiological  Standardization  o,f  (Pearson)   61 

Hediorite   136 

Hydrastine  in  Hemorrhage  of  the  Lung   429 

Hydrastis  Farming    525 

Hydrogen  Peroxide   281 

Hydroxyphenylethylamin    136 

Hyoscine  (DuMez)   339 

Hyoscyamus  and  Belladonna  (Newcomb)   531 

Hypochlorite-treated  Water  Supplies    143 

Hypophosphite  Fallacy,  The   281 

• 

Idomenin    429 

Insecticides  and  Fungicides  Abolished,  Legend  and  Serial  Number  on.  . . .  337 

International  Opium  Conference   274 

Ipecac    563 

Ipecacuanha    281 

Iron  Iodide,  A  Note  on  the  Value  of  the  Preservatives  in  Syrup  of 

(Beringer)     358 

Iron  in  the  Presence  of  Phosphoric  Acid,  The  Determination  of   423 


574  Index.  \      J?ur-  ^fm- 

%}/ ^  \  December,  1914. 

Jatropha  Urens,  The  Poisonous  Nature  of  the  Stinging  Hairs  of   527 

Kieselguhr  Industry   482 

Lacpinin    566 

Lactic  Acid  Ferments   137 

Larkspur  Seed,  The  Insecticidal  Value  of  Fluidextract  of  (Williams)   414 

Lecithin,  a  Comprehensive  Review  on  the  Occurrence,  Physiology  and  the 

Importance  of  Lecithin  in  Metabolism  and  Nutrition   163 

Leukozon    282 

Liquid  Paraffin  .   137 

Lloyd's  Reagent,  Notes  on  the  Estimation  on  (Gordin  and  Kaplin)   461 

Luminal    429 

Magma  Bismuthi  (Muller)   11 

Magnesium  Sulphate,  Commercial  Standards  for  Dried   424 

Mate,  The  Use  of   430 

Medical  Museum    424 

Medicinal  Preparations,  Department  of  Agriculture  Discusses  Objection- 
able Labelling  for   523 

Mercuric  Benzoate   563 

Mercuric  Chlorid  Tablets,  Assay  of  (Chapin)   1 

Mercuric  Salts,  Relative  Bactericidal  Power  of  ,   430 

Mercury  Tablets,  Bichloride  of,  and  Bichloride  Legislation  (Beringer)..  313 

Mineral  Constituents  of  Certain  Tinctures  and  Drugs   422 

Morphine  Addiction    564 

in  Pills,  Tablets,  etc.,  The  Estimation  of  (Williams)   308 

Notes  on  the  Estimation  of  (Gordin  and  Kaplan)   461 

Museum,  Medical,  Historical   132 

National  Association  of  Retail  Druggists,  News  Item   434 

Neohexal    566 

Neosalvarsan   .   283 

New  and  Non-official  Remedies   276 

Nitroglycerin,  Notes  on  the  Estimation  of  (Heyl  &  Staley)   195 

Tablets,  Determination  of   186 

Nitrous   140 

Novotryposafrol    282 

Nux  Vomica  and  Strychnine  with  Alkalies,  Iodides,  and  Bromides  ....  422 

Obituaries  : 

Ellis,  Evan  Tyson    96 

Fox,  Peter  P   480 

Ross,  David  H.  .   480 

Oil  of  Argemone  Mexicana  (Bhaduri)   49 

Russian  Mineral  (Puckner)   322 

of  Sandalwood  (Holmes)   31 

White  Mineral  '(Hilton)   360 

Opii,  Liquor,  Sedative   424 

Opium    138 

Conference,  The  Hague  :. ...  425 

Habit   425 

Smoking    425 

Suppression   425 

Orange,  Osage,  Its  Value  as  a  Commercial  Dyestuff   386 

Orthoform    566 

Papain,  Commercial,  and  its  Assay   564 

Commercial,  Standardization  of  (Heyl,  Caryl  and  Staley)    542 


Am.  Jour.  Pharm.  1  IiaApv  C1C 

December,  1914.   J  IfiaeX.  575 

Paraffin  in  Cancer    431 

Liquid  137,  282 

The  Sterilization  of   430 

Oil,  Renewed  Interest  in  ( Wilbert)   150 

Parakodin    566 

Patent  for  Complex  Medicine   133 

Patent  Medicine  Business,  The  419,  442 

Problem,  The  (Wilbert)  '   256 

Pennsylvania  State  Pharmaceutical  Association,  Abstracts  of  Some  Papers 

Read  at  the  1913  Meeting  of  the  (Thum)   37 

Pepsin  Bacteriologically  Considered,  The  Purity  of   421 

Perhydrit   138 

Perydal    282 

Petrolatum,  Liquid    430 

(Puckner)    322 

Liquidum,  U.  S.  P.  VIII  (Paraffinum  Liquidum)  (Hilton)   360 

Pharmaceutical  Associations,  National,  Annual  Meetings  of   275 

State,  Annual  Meetings  of   275 

Conference,  British   421 

Meeting  96,  242 

Organizations,  A  Plea  for  More  Effective  Co-operation  Among  (Day)  263 

Pharmaceutisch  Weekblad    278 

Pharmacists,  Laboratory  Equipment  of   276 

Pharmacognosy,  Applied  (Rippetoe)   114 

Pharmacy,  History  of   133 

Pharmacopoeia,  British    132,  420,  559 

Japanese    131 

National  Insurance    420 

U.  S.  IX    288,  290 

U.  S.,  A  Criticism  of  (DuMez)   339 

Phenol  in  Hydrocarbons,  Note  on  the  Solubility  of  (Pilcher)   149 

Phenolphthalein    282 

A  New  Method  for  the  Determination  of  (Mirkin)   307 

Phenolphthalein-agar    282 

Phenolsulphonephthalein    138 

Phenoval    138 

Philadelphia  College  of  Pharmacy  : 

Abstracts  from  the  Minutes  of  the  Board  of  Trustees.  ...  91,  226, '279,  520 

Annual  Meeting  ;   226 

Minutes  of  December  Meeting   91 

Minutes  of  Pharmaceutical  Meeting. .  ,   96 

Minutes  of  Quarterly  Meeting  '.   379 

Semi-annual  Meeting    520 

Ninety-third  Annual  Commencement   329 

President's  Annual  Address   226 

The  Cla)rton  French  Fellowship  in   245 

Phosphorus,  Amorphous    278 

Toxicity  of,  Influence  of  Diet  on  the   431 

Picric  Acid  in  Urine,  Detection  of   431 

Pikrastol   138 

Pituitary  Extract   431 

Pressor  Compounds,  Contribution  to  the  Chemistry  of  (Crawford 

and  Ostenberg)    291 

Poisoning  in  Great  Britain;  Death  by   426 

Responsibility  for   426 

Unusual  Case  of,  from  the  Administration  of  Male-Fern  as  a  Vermi- 
fuge  429 

Poison  Ivy,  The  Volatile  Nature  of  the  Toxic  Constituent  of  (Bessey)..  112 
Poisons,  Legislation  Concerning    562 


576 


Index. 


(  Am.  Jour.  Pharm. 
\    December,  1914. 


Pollantin,  Supply  of,  Affected  by  War   482 

Prescriptions    4x9 

Price  Maintenance    274 

Procter  Memorial,  An  Appreciation  (Remington)   243 

Monument,  The  Frontispiece,  Designed  by  Edward  Berge   243 

Progress  in  Pharmacy  (Wilbert)    128,  272,  416,  558 

Proprietary  Medicines  in  Great  Britain   132 

Remedies   420 

Pure  Drugs  and  the  Pharmacist   27K 

Public  Health  (Wilbert)   .'.WW.'.'  550 


Quinine    138 

and  Urea  Hydrochloride   139 

in  Malaria,  Prophylactic  Use  of   431 

in  Tablets,  An  Assay  Process  for  (Fieselmann)   54 

in  the  Treatment  of  Syphilis   432 

Poisoning   283 

Quinine-urea  Hydrochloride   283 

Rabies  and  the  Pasteur  Treatment   139 

Radium    139 

and  Radium  Salts    190 

in  Australia    139 

in  Cancer,  Results  of   432 

Treatment  of  Cancer,  Dangers  from   432 

Reaction,  Wassermann,  in  Tuberculosis   434 

Recordin   .   433 

Remedies,  Proprietary   561 

Reviews,  Book  : 

A  Handbook  of  Useful  Drugs   45 

Allen's  Commercial  Organic  Analysis   184 

American  Medical  Association,  Annual  Report  of  the  Investigations 
Carried  Out  Under  the  Supervision  of  the  Therapeutic  Research 

Committee  of  the  Council  on  Pharmacy  and  Chemistry  of  the   378 

Bastedo,  Walter  A.    Materia  Medica,  Pharmacology,  Therapeutics, 

Prescription  Writing,  for  Students  and  Practitioners   88 

Craig,  Charles  F.,  and  Henry  J.  Nichols.    Studies  on  Syphilis   47 

Eggleston,  Cary.    Essentials  of  Prescription  Writing   48 

Maiden,  J.  H.    A  Critical  Revision  of  the  Genus  Eucalyptus   479 

Merck's  Report  of  Recent  Advances  in  Pharmaceutical  Chemistry 

and  Therapeutics    142 

Motter,  Murray  Gait,  and  M.  I.  Wilbert.    Digest  of  Comments  on  the 
Pharmacopoeia  of  the  United  States  of  America,  and  on  the  National 

Formulary  for  the  Calendar  Year  Ending  December  31,  1911   39 

New  and  Non-official  Remedies   224 

Nichols,  Henry  J.,  and  Charles  F.  Craig.    Studies  on  Syphilis   47 

Payne,  George  F.    Payne's  Dictionary  of  Pharmacy   87 

Reports  of  the  Council  on  Pharmacy  and  Chemistry  of  the  American 

Medical  Association  for  1913,  Reprint  of  the   223 

Schenck,  Henry.    Chemical  Reagents   477 

Schimmel  &  Co.    Report  on  Essential  Oils   85 

Scoville,  Wilbur  L.    The  Art  of  Compounding   476 

Scudder,  Heyward.    The  Electrical  Conductivity  and  Ionization  Con- 
stants of  Organic  Compounds    477 

The  Propaganda  for  Reform  in  Proprietary  Medicines.   40 

Thorns,  H.    Arbeiten  aus  dem  Pharmazeutischen  Institut  der  Uni- 
versitat,  Berlin   42 


,Am.  Jour.  Pharm.  1 

'"[December,  1914.  J 


Index. 


577 


Wilbert,  M.  L,  and  Murray  Gait  Motter.    Digest  of  Comments  on  the 
Pharmacopoeia  of  the  United  States  of  America  and  on  the  National 


Formulary  for  the  Calendar  Year  Ending  December  31,  191 1   39 

Youngken,  Heber  W.    Pharmaceutical  Botany   223 

Rhamnus  Purshiana,  Its  History,  Growth,  Methods  of  Collection  and 

Bibliography  (Johnson  and  Hindman)   387 

Rhodoform    566 

Riopan    283 

Rhubarb  ,  433 

Saccharin  and  Analogous  Substances,  The  Control  of   433 

Saffron   139 

Salt  Solution,  The  Abuse  of  Normal   430 

New  Technic  for   430 

Salvarsan    140,  283 

Sarsaparilla   # . .  284 

Scillitin,  The  Toxic  Principle  of  Squill   433 

Scopolamine  (DuMez)    339 

in  Ampoules,  Pharmacological  Instability  of   432 

Solution   140 

Seasonable  Variations  in  the  Resistance  of  Guinea  Pigs  to  Poisoning  by 

Ouabain  and  by  Liquid  Preparations  of  Digitalis  (Haskell)   7 

Senna,  Constituents  of    288 

Sennatin   433 

Serum,  Antimeningitis    427 

Treatment  of  Hay  Fever   289 

Treatment  of  Tetanus    284 

Silks,  The  Identification  of  Artificial,  Especially  Prepared  for  the  Practical 

Mill  Man  and  Dyer  (Matos)   471 

Silver  Methylene  Blue    284 

Silver  Salts,  Organic    138 

Sleep,  What  is?    242 

Soap,  What  is?   '   187 

Sodium  Phosphate,  Commercial  Standards  for  Dried   424 

Sulphate,  Commercial  Standards  for  Dried   424 

Spirit  of  Nitrous  Ether   140 

Starch,  The  Influence  of  Heat  and  Chemicals  on  the  Grain  of  (Kraemer)  .  81 
Strychnine  and  Nux  Vomica  with  Alkalies,  Iodides,  and  Bromides,  The 

Incompatibility  of   422 

in  the  Presence  of  Brucine,  Estimation  of   421 

Suicides  and  Newspaper  Publicity    562 

Sulphates,  The  Volumetric  Estimation  of  (Worth)   249 

Synthetics,  Coal-Tar,  Restriction  of  Sale  of    130 

Syrups,  Fermentation  of    140 

Tablet  Industry,  The,  its  Evolution  and  Present  Status,  the  Composition 

of  Tablets  and  Methods  of  Analysis   433 

Compressed    434 

Temosin   284 

Theobromine  Sodium  Salicylate   284 

Theoform   141 

Thiophysein    566 

Thymolphthalein   141 

Thyroideum  Siccum    141 

Tinctura  Iodi  Decolorata,  The  Composition  of   423 

Tincture  Press,  Some  Uses  of  a   424 

Tobacco  Snuff   285 

Tricarbin    285 

Tuberculosis,  Calcium  Therapy  of  .'   427 


Index. 


{Am.  Jour.  Ph»rm. 
December,  1914. 


Turpentine,  Warning  to  Users  of   194 

Tyrene    141 

Ulsanin   141 

Uranium,  Metallic,  Production  of   432 

Urease  ;   434 

Urotropin    434 

Uteramin    434 

U.  S.  P.  1900  Menstrua  (Hamilton)   56 

Revision   418 

U.  S.  Public  Health  Service  (Anderson)   155 

Vaccine    141 

Vaccines,  A  Consideration  of  Autogenous  (Lyon)   206 

Vitamines    285 

The.    The  Recognition  of  Essential  Constituents  of  the  Diet  Hitherto 

Unclassified.    Deficiency  Diseases   (Stiles)   237 

Vleminckx's  Solution,  Preparation  and  Analyses  of  (Mayer)   355 


Weights  and  Measures   276,  419 

Zinc  Stearate,  The  Assay  of  (Gesell)   120 

Zymase     142 


i 


® 


Bound  JUL  1  7  1915 


Salt  A